Neurobiology of Epileptogenesis

Size: px
Start display at page:

Download "Neurobiology of Epileptogenesis"

Transcription

1

2 Neurobiology of Epileptogenesis Michael C. Smith, MD Director, Rush Epilepsy Center Professor and Senior Attending Neurologist Rush University Medical Center Chicago, IL

3 Network Milieu Cellular Milieu Synaptic Milieu Molecular Milieu Molecular, Synaptic, and Cellular Effects of Seizures SEIZURE seconds-to-minutes hours-to-days weeks-months-years Intracellular Extracellular Presynaptic Element (Axon Terminals) Postsynaptic Element (Receptors/Channels) Presynaptic- Postsynaptic Functional Unit Ca++ Enzyme Activity Adenosine K+ Glutamate Excitation GABA Inhibition Facilitation PTP LTP Gene Expression Nerve Growth Factors Axon Proliferation, Growth 1 Synaptogenesis Kainate Receptors BZD Receptors Glia Neurons Necrosis Neuron Loss Apoptosis Gliosis Local Circuit Excitation > Inhibition Imbalance Projection Circuit Disconnection Between Regions Lothman EW. Epilepsy: Models, Mechanisms, and Concepts

4 Basic Mechanisms of Seizures Neuronal short-circuit - PDS Paroxysmal Depolarization Shift Neuronal synchronization Gap junctions, ephaptic coupling, electrical fields, ionic concentrations Transition from interictal to ictus Failure of inhibition, excessive excitation

5 Paroxysmal Depolarization Shift Paroxysmal Depolarization Shift (PDS) is described in both experimental animal models of epilepsy and in human tissue obtained in epilepsy surgery Intracellular expression of epileptic spike Well-characterized with micro-electrode studies

6 Na + influx Ca +2 influx Paroxysmal Depolarization Shift Paroxysmal depolarization shift o Vm Vth Vrest -70 mv TIME Voltage dependent K + efflux Ca + 2 dependent 200 msec

7 Paroxysmal Depolarization Shift Pathophysiology of PDS Abnormal ionic conductance (Na + /Ca ++ ) Due to increased number of ionic channels Excessive response to normal input Due to excessive excitatory input Giant EPSP (excitatory post-synaptic potential) Probably a combination of both

8 PDS Origin of Interictal Spike Intracellular recording Extracellular recording Paroxysmal depolarizing shift Wong PK, et al. Prog Brain Res

9 PDS Ionic Conductance A. Interictal PDS within seizure focus B. Basic cortical circuit Feed-forward inhibition Feedback inhibition Westbrook G. Principles of Neuroscience

10 Epileptic Focus Interplay Between Excitatory and Inhibitory Circuitry Westbrook G. Principles of Neuroscience

11 Neurobiology of Absence Seizures A EEG Neuron GABA GABA GABA GABA T-Ca ++ T-Ca ++ T-Ca ++ 1 sec B Cortex Thalamus T R T R Re Nu Dichter MA. Epilepsia

12 Neuronal Synchronization Poorly understood and difficult to study Synchronization is necessary to reach the critical mass of neurons to overwhelm normal surround inhibition for transition to ictus There are multiple mechanisms responsible for neuronal synchronization

13 Neuronal Synchronization Neuronal synchronization may occur at dendritic and axonal levels, but not at cell body Gap junctions on these processes, when blocked, prevent fast ripple potentials that synchronize adjacent neurons Electrical field effects may synchronize adjacent neurons Alterations in extracellular space and ionic concentrations affect neuronal excitability and synchronization Scharfman HE. Curr Neurol Neurosci Rep

14 Interactions Between NMDA Activation, Extracellular Space and Potassium Concentration Spike threshold Burst AHP Depolarization IPSP NMDA receptor NEURONAL FIRING DURING INTERICTAL BURSTS Cell swelling EC space Ephaptic coupling RISE IN BASELINE [K + ] Larger [K + ] transient during interictal burst Seizure

15 Effects of Seizure on Extracellular Space and Ionic Concentration Lothman EW. Epilepsy: Models, Mechanisms, and Concepts

16 Glial Cell - Role in Generation and Spread of Seizures Impaired K + buffering due to reduced gk(ir) in sclerotic epileptic hippocampus Enhanced expression of astroglial gap junction protein supports hypersynchronization Enhanced activation of metabotropic glutamate receptors with increased intracellular Ca ++ Steinhäuser C. Eur J Pharmacol

17 Astrocytic Ionic Regulatory Function Steinhäuser C. Eur J Pharmacol

18 Pathophysiology of Interictal Spike Interictal discharge Originating in temporal lobe Excitatory Center Inhibitory surround Pyramidal Cells Basket cells Synaptic inhibition in surrounding neurons DS Hyperpolarization Dichter MA. Epilepsia

19 Transition to Ictus Imbalance of excitation and inhibition Failure of inhibition: Activity dependent disinhibition Loss of the after hyperpolarization (AHP) Loss of surround inhibition Excessive glutamate stimulation Positive feedback Recurrent excitatory feedback circuitry Staley K. Nat Neurosci. 2015; Scharfman HE. Curr Neurol Neurosci Rep

20 Transition from Interictal State to Ictus Tonic Phase Clonic Phase Seizure Focus Distant Lothman EW. Epilepsy: Models, Mechanisms, and Concepts

21 GABA Desensitization Leading to Inhibitory Failure

22 Glutamate Neurotransmission Dichter MA. Epilepsia

23 Excessive Excitation Breaking Down Inhibition

24 Seizure-induced Change in Neuron Function and Structure Lothman EW. Epilepsy: Models, Mechanisms, and Concepts

25 An 18-month old male has a 25 minute convulsion followed by R-sided Todd s Paralysis. The following may occur: A. Excitotoxic damage to the dentate gyrus B. Neuronal reorganization leading to hyperexcitable hippocampus C. Increased risk of later seizures D. All of the above

26 Example of Excitotoxicity in Hippocampus after Status Epilepticus

27 Important Factors in Epileptogenesis Alteration/expression/membrane localization in GABAA subunits resulting in changes in phasic/tonic inhibition and response to modulators (BZD/Zn) Up-regulation of NMDA and AMPA is seen in both models of epileptogenesis and from TLE pathology Reorganization of neuronal networks Brooks-Kayal AR, et al. J Neurosci. 1999; Stasheff SF, et al. Science. 1989; Sharfman HE. Prog Brain Res

28 Synaptic Reorganization Resulting in Hyperexcitability and Epilepsy Seizures result in neuronal death of the hilar dentate neurons The hilar dentate neuron is the target of the dentate granule mossy fiber axon These fibers seek new synaptic contacts, at times, reinnervating themselves resulting in a recurrent positive feedback loop Tauck DL, et al. J Neurosci. 1985; Sutula T, et al. Science ;Sharfman Prog Brain Res,2007

29 Hippocampal Reorganization Holmes MM, et al. Behav Neurosci

30 Synaptic Reorganization Resulting in Hyperexcitability and Epilepsy Hyperexcitability is due to the loss of feed forward inhibition due to loss of excitatory input to the inhibitory basket cell Loss of the inhibitory neurons feedback inhibition Probably all three mechanisms are involved Sloviter RS, et al. Science

31 Changes in Synaptic Connectivity in Epilepsy Sloviter RS, et al. Science

32 Hippocampal Epilepsy Dentate Gyrus as Gatekeeper A - Normal circuitry Dentate gyrus Parahippocampal gyrus Hippocampus Hippocampus Dentate gyrus _ + + _ G BC + BC Mossy cell Dentate gyrus Parahippocampal gyrus B -Temporal lobe epilepsy Dentate gyrus _ + + _ G BC + BC Mossy cell Hippocampus Dentate gyrus Parahippocampal gyrus Sloviter RS. Ann Neurol

33 Receptor Activation During Seizure Tonic-Clonic Electrographic Paroxysm EEG Neuron AMPA GABA NMDA 1sec Non-T Ca ++ Primary Epileptogenic Zone Zone of Dissemination Lothman EW. Epilepsy: Models, Mechanisms, and Concepts

34 Inflammation in Experimental Models In many animal models of epilepsy and acute seizures there is up-regulation of inflammation with microglial activation and increased expression of transcription factors and cytokines that help coordinate the inflammatory response Toll-like receptor (TLR) family upregulated in microglia leading to transcriptional activation of cytokines, chemokines in the MHC class I and II This contributes to the seizure-related neuronal death and neuronal reorganization seen in hippocampal epilepsies Zimmer LA, et al. J Comp Neurol. 1997; Turrin NP, et al. Neurobiol Dis

35 Breakdown of BBB In mice, CNS infection with LCMV results in seizures and death CD8+ T cells recognize LCMV infected cells, bind to them and kill them CD8+ T cells secrete chemokines, which trigger influx of myeloid cells and breakdown of BBB Depleting the myeloid cells delays seizures and death, suggesting a causal role of inflammation, breakdown of BBB, and fatal seizures LCMV=lymphocytic choriomeningitis virus Kim JV, et al. Nature

36 Breakdown of BBB Pilocarpine model of experimental seizures and epilepsy Pilocarpine results in transient adherence between WBCs and endothelial cells of BBB resulting in a leaky BBB This permits albumin and other proteins to cross the BBB causing down regulation of astrocytic K+ channels, disrupting K+ homeostasis producing seizures and epilepsy. Seizures induce angiogenesis with porous BBB. Suppressing this interaction between WBC and endothelial cells and porous BBB prevented seizures and progression to epilepsy Fabene PF, et al. Nat Med. 2008; Ivens S, et al. Brain. 2007; Rigau V, et al. Brain

37 Paraneoplastic/Autoimmune Encephalitis Clinical phenotype Myelitis, limbic or brainstem encephalitis Antibodies intracellular proteins ie, anti-hu, anti-ma2, anti CRMPs encephalomyelitis Antibodies to synaptic proteins ie, anti-nmda, anti-ampa, LG1 antibody, anti-gaba A,B, anti-caspar2, anti-lgi1 Treatment: Steroids, IVIG, PLEX, remove tumor. If no response rituximab, cyclophosphamide Graus F, et al. Lancet Neurol

38 Epilepsy and Other Chronic Convulsive Diseases Every fit, slight or severe, is in some degree the effect of those which precede it, the cause of those that follow it. Gowers WR

39 Pathophysiology of Epilepsy ONTOGENY EPILEPTOGENESIS Lothman EW. Epilepsy: Models, Mechanisms, and Concepts

40 Epileptogenesis Genetics Initiating Event Critical modulators Structural/ Functional changes Clinical Seizures CHRONIC EPILEPSY Age Refractory Epilepsy? Neurobehavioral changes, Cognitive impairment? Latent Period

41 Basic Mechanisms of Epilepsy Seizures beget seizures Kindling model of epilepsy Model of partial epilepsy as well as neuronal learning Chronic epilepsy is maladaptive learning Prevent, rather than treat, intractable epilepsy Gowers WR

42 Anticonvulsant Agents Identified by maximal electroshock or metrazol models Stop expression or spread of seizures Na + channel/gaba mechanism of action Little effect on interictal spiking No effect on epileptogenesis (development of seizures) as judged by the kindling model of epilepsy

43 Antiepileptogenic Agent Affects the development with variable effects on the expression of seizures Interferes with the development of kindling Suppresses interictal spiking Action via glutamate mechanisms/ca ++? Protects neuronal circuits from the deleterious effects of epileptic discharges

44 Kindling Model of Epilepsy In 1967, Goddard reported on a new phenomenon he called kindling : Electrical stimulation in the rat amygdala that initially produced no clinical change in the animals behavior but did produce an after discharge (AD) if repeated daily days produced a permanent epileptic condition Goddard GV. Nature

45 EEG: Kindling; Day Prolongation and Spread of the AD Day 1 Day 6 Day 14

46 Kindling Model Widespread effects on neurotransmitters, receptors, neuronal processes, and gene expression Potentiation EPSP in stimulated pathway Long term potentiation (LTP) occurs early in the kindling process This allows better coupling between EPSP and neuronal output Goddard GV. Nature. 1967; Bertram E. Epilepsia

47 This residual disposition to repetition of the same activity is the physical basis of memory, of muscular training, of all cerebral education and it is the basis of the morbid education of the brain which underlies epilepsy. Gowers WR

48 Kindling Model Only model to allow a quantitative analysis of epileptogenesis and its prevention with AEDs Study the effect of AED on AD length and the number of electrical stimulations to reach a certain seizure stage Model for SPS, CPS, and CPS with secondary generalization Bertram E. Epilepsia

49 AEDs Effect on Epileptogenesis Sodium channel blockers treat kindled seizure but do not inhibit the kindling process Sodium channel blockers (DPH,CBZ) offer no prophylaxis in the development of epilepsy Valproate, levetiracetam, and perhaps zonisamide, topiramate, and perampanel blunt the epileptogenic process as judged by the kindling model? Prevents the development of epilepsy

50 Conclusions Understanding the basic mechanisms of seizures allows increased understanding of the MOA of our AEDS and offers additional treatment targets in the treatment of seizures (ie, gap junction blockers). Understanding basic mechanisms of epilepsy offers novel treatment options that may prevent the development of intractable epilepsy and its cognitive and behavioral sequelae.

epilepticus (SE) or trauma. Between this injury and the emergence of recurrent

epilepticus (SE) or trauma. Between this injury and the emergence of recurrent Introduction Epilepsy is one of the oldest medical disorders known. The word epilepsy derived from the Greek word epilamhanein, meaning to be seized or to be overwhelmed by surprise. Epilepsy is one of

More information

Intracranial Studies Of Human Epilepsy In A Surgical Setting

Intracranial Studies Of Human Epilepsy In A Surgical Setting Intracranial Studies Of Human Epilepsy In A Surgical Setting Department of Neurology David Geffen School of Medicine at UCLA Presentation Goals Epilepsy and seizures Basics of the electroencephalogram

More information

Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical

Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical Are There Sharing Mechanisms of Epilepsy, Migraine and Neuropathic Pain? Chin-Wei Huang, MD, PhD Department of Neurology, NCKUH Basic mechanisms underlying seizures and epilepsy Seizure: the clinical manifestation

More information

Antiepileptic agents

Antiepileptic agents Antiepileptic agents Excessive excitability of neurons in the CNS Abnormal function of ion channels Spread through neural networks Abnormal neural activity leads to abnormal motor activity Suppression

More information

Synaptic Integration

Synaptic Integration Synaptic Integration 3 rd January, 2017 Touqeer Ahmed PhD Atta-ur-Rahman School of Applied Biosciences National University of Sciences and Technology Excitatory Synaptic Actions Excitatory Synaptic Action

More information

MOLECULAR AND CELLULAR NEUROSCIENCE

MOLECULAR AND CELLULAR NEUROSCIENCE MOLECULAR AND CELLULAR NEUROSCIENCE BMP-218 November 4, 2014 DIVISIONS OF THE NERVOUS SYSTEM The nervous system is composed of two primary divisions: 1. CNS - Central Nervous System (Brain + Spinal Cord)

More information

How Synapses Integrate Information and Change

How Synapses Integrate Information and Change How Synapses Integrate Information and Change Rachel Stewart class of 2016 http://neuroscience.uth.tmc.edu/s1/chapter06.html http://neuroscience.uth.tmc.edu/s1/chapter07.html Chris Cohan, Ph.D. Dept. of

More information

Synaptic Transmission: Ionic and Metabotropic

Synaptic Transmission: Ionic and Metabotropic Synaptic Transmission: Ionic and Metabotropic D. Purves et al. Neuroscience (Sinauer Assoc.) Chapters 5, 6, 7. C. Koch. Biophysics of Computation (Oxford) Chapter 4. J.G. Nicholls et al. From Neuron to

More information

How Synapses Integrate Information and Change

How Synapses Integrate Information and Change How Synapses Integrate Information and Change Rachel Stewart class of 2016 https://nba.uth.tmc.edu/neuroscience/s1/chapter06.html https://nba.uth.tmc.edu/neuroscience/s1/chapter07.html Chris Cohan, Ph.D.

More information

Chapter 2: Cellular Mechanisms and Cognition

Chapter 2: Cellular Mechanisms and Cognition Chapter 2: Cellular Mechanisms and Cognition MULTIPLE CHOICE 1. Two principles about neurons were defined by Ramón y Cajal. The principle of connectional specificity states that, whereas the principle

More information

Inflammation in epileptogenesis after traumatic brain injury

Inflammation in epileptogenesis after traumatic brain injury Webster et al. Journal of Neuroinflammation (2017) 14:10 DOI 10.1186/s12974-016-0786-1 REVIEW Open Access Inflammation in epileptogenesis after traumatic brain injury Kyria M. Webster 1, Mujun Sun 1, Peter

More information

SYNAPTIC COMMUNICATION

SYNAPTIC COMMUNICATION BASICS OF NEUROBIOLOGY SYNAPTIC COMMUNICATION ZSOLT LIPOSITS 1 NERVE ENDINGS II. Interneuronal communication 2 INTERNEURONAL COMMUNICATION I. ELECTRONIC SYNAPSE GAP JUNCTION II. CHEMICAL SYNAPSE SYNAPSES

More information

Neuroscience: Exploring the Brain, 3e. Chapter 4: The action potential

Neuroscience: Exploring the Brain, 3e. Chapter 4: The action potential Neuroscience: Exploring the Brain, 3e Chapter 4: The action potential Introduction Action Potential in the Nervous System Conveys information over long distances Action potential Initiated in the axon

More information

Applied Neuroscience. Conclusion of Science Honors Program Spring 2017

Applied Neuroscience. Conclusion of Science Honors Program Spring 2017 Applied Neuroscience Conclusion of Science Honors Program Spring 2017 Review Circle whichever is greater, A or B. If A = B, circle both: I. A. permeability of a neuronal membrane to Na + during the rise

More information

Correlated network activity in the developing hippocampus: role in synaptogenesis

Correlated network activity in the developing hippocampus: role in synaptogenesis Enrico Cherubini Correlated network activity in the developing hippocampus: role in synaptogenesis SPACE PHYSICS and BIOLOGY Dubna, December 19-23, 2010 The construction of the brain relies on genetic

More information

NEURONS COMMUNICATE WITH OTHER CELLS AT SYNAPSES 34.3

NEURONS COMMUNICATE WITH OTHER CELLS AT SYNAPSES 34.3 NEURONS COMMUNICATE WITH OTHER CELLS AT SYNAPSES 34.3 NEURONS COMMUNICATE WITH OTHER CELLS AT SYNAPSES Neurons communicate with other neurons or target cells at synapses. Chemical synapse: a very narrow

More information

Part 11: Mechanisms of Learning

Part 11: Mechanisms of Learning Neurophysiology and Information: Theory of Brain Function Christopher Fiorillo BiS 527, Spring 2012 042 350 4326, fiorillo@kaist.ac.kr Part 11: Mechanisms of Learning Reading: Bear, Connors, and Paradiso,

More information

Human Brain and Senses

Human Brain and Senses Human Brain and Senses Outline for today Levels of analysis Basic structure of neurons How neurons communicate Basic structure of the nervous system Levels of analysis Organism Brain Cell Synapses Membrane

More information

Disclosures. Mechanism of Action Importance. Advances in Epilepsy Management: Does Mechanism-of- Action Matter?

Disclosures. Mechanism of Action Importance. Advances in Epilepsy Management: Does Mechanism-of- Action Matter? Advances in Epilepsy Management: Does Mechanism-of- Action Matter? Barry E. Gidal, PharmD University of Wisconsin-Madison School of Pharmacy & Dept. of Neurology Disclosures Speaking honoraria: UCB, Eisai,

More information

BIPN 140 Problem Set 6

BIPN 140 Problem Set 6 BIPN 140 Problem Set 6 1) Hippocampus is a cortical structure in the medial portion of the temporal lobe (medial temporal lobe in primates. a) What is the main function of the hippocampus? The hippocampus

More information

Memory Systems II How Stored: Engram and LTP. Reading: BCP Chapter 25

Memory Systems II How Stored: Engram and LTP. Reading: BCP Chapter 25 Memory Systems II How Stored: Engram and LTP Reading: BCP Chapter 25 Memory Systems Learning is the acquisition of new knowledge or skills. Memory is the retention of learned information. Many different

More information

9/28/2016. Neuron. Multipolar Neuron. Astrocytes Exchange Materials With Neurons. Glia or Glial Cells ( supporting cells of the nervous system)

9/28/2016. Neuron. Multipolar Neuron. Astrocytes Exchange Materials With Neurons. Glia or Glial Cells ( supporting cells of the nervous system) Neuron Multipolar Neuron https://www.youtube.com/watch?v=lw-psbnu5xago to :38 Glia or Glial Cells ( supporting cells of the nervous system) 10X more numerous than neurons but one-tenth the size make up

More information

Communication within a Neuron

Communication within a Neuron Neuronal Communication, Ph.D. Communication within a Neuron Measuring Electrical Potentials of Axons The Membrane Potential The Action Potential Conduction of the Action Potential 1 The withdrawal reflex

More information

BIPN 140 Problem Set 6

BIPN 140 Problem Set 6 BIPN 140 Problem Set 6 1) The hippocampus is a cortical structure in the medial portion of the temporal lobe (medial temporal lobe in primates. a) What is the main function of the hippocampus? The hippocampus

More information

Chapter 2. The Cellular and Molecular Basis of Cognition Cognitive Neuroscience: The Biology of the Mind, 2 nd Ed.,

Chapter 2. The Cellular and Molecular Basis of Cognition Cognitive Neuroscience: The Biology of the Mind, 2 nd Ed., Chapter 2. The Cellular and Molecular Basis of Cognition Cognitive Neuroscience: The Biology of the Mind, 2 nd Ed., M. S. Gazzaniga, R. B. Ivry, and G. R. Mangun, Norton, 2002. Summarized by B.-W. Ku,

More information

The Nervous System. Nervous System Functions 1. gather sensory input 2. integration- process and interpret sensory input 3. cause motor output

The Nervous System. Nervous System Functions 1. gather sensory input 2. integration- process and interpret sensory input 3. cause motor output The Nervous System Nervous System Functions 1. gather sensory input 2. integration- process and interpret sensory input 3. cause motor output The Nervous System 2 Parts of the Nervous System 1. central

More information

The Cerebral Cortex and Higher Intellectual Functions

The Cerebral Cortex and Higher Intellectual Functions The Cerebral Cortex and Higher Intellectual Functions The Cerebral cortex consists of 2 cerebral hemisphere and each hemisphere consists of 5 lobes (frontal, parietal,temporal,occipital,insular lobe which

More information

Neurons. Pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons.

Neurons. Pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons. Neurons Pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons. MBL, Woods Hole R Cheung MSc Bioelectronics: PGEE11106 1 Neuron

More information

Nervous System. Master controlling and communicating system of the body. Secrete chemicals called neurotransmitters

Nervous System. Master controlling and communicating system of the body. Secrete chemicals called neurotransmitters Nervous System Master controlling and communicating system of the body Interacts with the endocrine system to control and coordinate the body s responses to changes in its environment, as well as growth,

More information

Organization of the nervous system. [See Fig. 48.1]

Organization of the nervous system. [See Fig. 48.1] Nervous System [Note: This is the text version of this lecture file. To make the lecture notes downloadable over a slow connection (e.g. modem) the figures have been replaced with figure numbers as found

More information

8 Epilepsy-Based Changes in Hippocampal Excitability: Causes and Effects

8 Epilepsy-Based Changes in Hippocampal Excitability: Causes and Effects 8 Epilepsy-Based Changes in Hippocampal Excitability: Causes and Effects L. Stan Leung and Kun Wu * Departments of Physiology-Pharmacology and Clinical Neurological Sciences and Neuroscience Graduate Program,

More information

Chapter 2. The Cellular and Molecular Basis of Cognition

Chapter 2. The Cellular and Molecular Basis of Cognition Chapter 2. The Cellular and Molecular Basis of Cognition Cognitive Neuroscience: The Biology of the Mind, 2 nd Ed., M. S. Gazzaniga,, R. B. Ivry,, and G. R. Mangun,, Norton, 2002. Summarized by B.-W. Ku,

More information

Introduction to Neurobiology

Introduction to Neurobiology Biology 240 General Zoology Introduction to Neurobiology Nervous System functions: communication of information via nerve signals integration and processing of information control of physiological and

More information

BIPN100 F15 Human Physiology 1 Lecture 3. Synaptic Transmission p. 1

BIPN100 F15 Human Physiology 1 Lecture 3. Synaptic Transmission p. 1 BIPN100 F15 Human Physiology 1 Lecture 3. Synaptic Transmission p. 1 Terms you should know: synapse, neuromuscular junction (NMJ), pre-synaptic, post-synaptic, synaptic cleft, acetylcholine (ACh), acetylcholine

More information

Chapter 11 Introduction to the Nervous System and Nervous Tissue Chapter Outline

Chapter 11 Introduction to the Nervous System and Nervous Tissue Chapter Outline Chapter 11 Introduction to the Nervous System and Nervous Tissue Chapter Outline Module 11.1 Overview of the Nervous System (Figures 11.1-11.3) A. The nervous system controls our perception and experience

More information

Glutamate Overview. How can one neurotransmitter have so many diverse functions?

Glutamate Overview. How can one neurotransmitter have so many diverse functions? tamate Overview How can one neurotransmitter have so many diverse functions? Darryle Schoepp, Ph.D. Senior Vice President and Franchise Head, Neuroscience Control of Excitability via Amino Acid Neurotransmitters

More information

Changes in Extracellular Ionic Composition q

Changes in Extracellular Ionic Composition q Changes in Extracellular Ionic Composition q JL Stringer, Baylor College of Medicine, Houston, TX, United States Ó 2017 Elsevier Inc. All rights reserved. Introduction 1 Background 1 Methods 2 Recent Results

More information

Lecture 22: A little Neurobiology

Lecture 22: A little Neurobiology BIO 5099: Molecular Biology for Computer Scientists (et al) Lecture 22: A little Neurobiology http://compbio.uchsc.edu/hunter/bio5099 Larry.Hunter@uchsc.edu Nervous system development Part of the ectoderm

More information

Neurons, Synapses and Signaling. Chapter 48

Neurons, Synapses and Signaling. Chapter 48 Neurons, Synapses and Signaling Chapter 48 Warm Up Exercise What types of cells can receive a nerve signal? Nervous Organization Neurons- nerve cells. Brain- organized into clusters of neurons, called

More information

Physiology of synapses and receptors

Physiology of synapses and receptors Physiology of synapses and receptors Dr Syed Shahid Habib Professor & Consultant Clinical Neurophysiology Dept. of Physiology College of Medicine & KKUH King Saud University REMEMBER These handouts will

More information

CSE 599E Lecture 2: Basic Neuroscience

CSE 599E Lecture 2: Basic Neuroscience CSE 599E Lecture 2: Basic Neuroscience 1 Today s Roadmap The neuron doctrine (or dogma) Neuronal signaling The electrochemical dance of ions Action Potentials (= spikes) Synapses and Synaptic Plasticity

More information

Chapter 4 Neuronal Physiology

Chapter 4 Neuronal Physiology Chapter 4 Neuronal Physiology V edit. Pg. 99-131 VI edit. Pg. 85-113 VII edit. Pg. 87-113 Input Zone Dendrites and Cell body Nucleus Trigger Zone Axon hillock Conducting Zone Axon (may be from 1mm to more

More information

Structure of a Neuron:

Structure of a Neuron: Structure of a Neuron: At the dendrite the incoming signals arrive (incoming currents) At the soma current are finally integrated. At the axon hillock action potential are generated if the potential crosses

More information

Na + K + pump. The beauty of the Na + K + pump. Cotransport. The setup Cotransport the result. Found along the plasma membrane of all cells.

Na + K + pump. The beauty of the Na + K + pump. Cotransport. The setup Cotransport the result. Found along the plasma membrane of all cells. The beauty of the Na + K + pump Na + K + pump Found along the plasma membrane of all cells. Establishes gradients, controls osmotic effects, allows for cotransport Nerve cells have a Na + K + pump and

More information

STRUCTURAL ELEMENTS OF THE NERVOUS SYSTEM

STRUCTURAL ELEMENTS OF THE NERVOUS SYSTEM STRUCTURAL ELEMENTS OF THE NERVOUS SYSTEM STRUCTURE AND MAINTENANCE OF NEURONS (a) (b) Dendrites Cell body Initial segment collateral terminals (a) Diagrammatic representation of a neuron. The break in

More information

Neurons, Synapses, and Signaling

Neurons, Synapses, and Signaling Neurons, Synapses, and Signaling The Neuron is the functional unit of the nervous system. Neurons are composed of a cell body, which contains the nucleus and organelles; Dendrites which are extensions

More information

Synaptic plasticityhippocampus. Neur 8790 Topics in Neuroscience: Neuroplasticity. Outline. Synaptic plasticity hypothesis

Synaptic plasticityhippocampus. Neur 8790 Topics in Neuroscience: Neuroplasticity. Outline. Synaptic plasticity hypothesis Synaptic plasticityhippocampus Neur 8790 Topics in Neuroscience: Neuroplasticity Outline Synaptic plasticity hypothesis Long term potentiation in the hippocampus How it s measured What it looks like Mechanisms

More information

Sleep-Wake Cycle I Brain Rhythms. Reading: BCP Chapter 19

Sleep-Wake Cycle I Brain Rhythms. Reading: BCP Chapter 19 Sleep-Wake Cycle I Brain Rhythms Reading: BCP Chapter 19 Brain Rhythms and Sleep Earth has a rhythmic environment. For example, day and night cycle back and forth, tides ebb and flow and temperature varies

More information

EEG Patterns of High dose Pilocarpine-Induced Status Epilepticus in Rats

EEG Patterns of High dose Pilocarpine-Induced Status Epilepticus in Rats Journal of the K. S. C. N. Vol. 2, No. 2 EEG Patterns of High dose Pilocarpine-Induced Status Epilepticus in Rats Kyung-Mok Lee, Ki-Young Jung, Jae-Moon Kim Department of Neurology, Chungnam National University

More information

EE 791 Lecture 2 Jan 19, 2015

EE 791 Lecture 2 Jan 19, 2015 EE 791 Lecture 2 Jan 19, 2015 Action Potential Conduction And Neural Organization EE 791-Lecture 2 1 Core-conductor model: In the core-conductor model we approximate an axon or a segment of a dendrite

More information

Synaptic Communication. Steven McLoon Department of Neuroscience University of Minnesota

Synaptic Communication. Steven McLoon Department of Neuroscience University of Minnesota Synaptic Communication Steven McLoon Department of Neuroscience University of Minnesota 1 Course News The first exam is next week on Friday! Be sure to checkout the sample exam on the course website. 2

More information

Action potential. Definition: an all-or-none change in voltage that propagates itself down the axon

Action potential. Definition: an all-or-none change in voltage that propagates itself down the axon Action potential Definition: an all-or-none change in voltage that propagates itself down the axon Action potential Definition: an all-or-none change in voltage that propagates itself down the axon Naturally

More information

Ameen Alsaras. Ameen Alsaras. Mohd.Khatatbeh

Ameen Alsaras. Ameen Alsaras. Mohd.Khatatbeh 9 Ameen Alsaras Ameen Alsaras Mohd.Khatatbeh Nerve Cells (Neurons) *Remember: The neural cell consists of: 1-Cell body 2-Dendrites 3-Axon which ends as axon terminals. The conduction of impulse through

More information

Portions from Chapter 6 CHAPTER 7. The Nervous System: Neurons and Synapses. Chapter 7 Outline. and Supporting Cells

Portions from Chapter 6 CHAPTER 7. The Nervous System: Neurons and Synapses. Chapter 7 Outline. and Supporting Cells CHAPTER 7 The Nervous System: Neurons and Synapses Chapter 7 Outline Neurons and Supporting Cells Activity in Axons The Synapse Acetylcholine as a Neurotransmitter Monoamines as Neurotransmitters Other

More information

When cells are already maximally potentiated LTP is occluded.

When cells are already maximally potentiated LTP is occluded. When cells are already maximally potentiated LTP is occluded. Stein, V et al., (2003) J Neurosci, 23:5503-6606. Also found in Rat Barrel Cortex Ehrlich & Malinow (2004) J. Neurosci. 24:916-927 Over-expression

More information

3) Most of the organelles in a neuron are located in the A) dendritic region. B) axon hillock. C) axon. D) cell body. E) axon terminals.

3) Most of the organelles in a neuron are located in the A) dendritic region. B) axon hillock. C) axon. D) cell body. E) axon terminals. Chapter 48 Neurons, Synapses, and Signaling Multiple-Choice Questions 1) A simple nervous system A) must include chemical senses, mechanoreception, and vision. B) includes a minimum of 12 ganglia. C) has

More information

Nervous System, Neuroanatomy, Neurotransmitters

Nervous System, Neuroanatomy, Neurotransmitters Nervous System, Neuroanatomy, Neurotransmitters Neurons Structure of neurons Soma Dendrites Spines Axon Myelin Nodes of Ranvier Neurons Structure of neurons Axon collaterals 1 Neurons Structure of neurons

More information

Summarized by B.-W. Ku, E. S. Lee, and B.-T. Zhang Biointelligence Laboratory, Seoul National University.

Summarized by B.-W. Ku, E. S. Lee, and B.-T. Zhang Biointelligence Laboratory, Seoul National University. Chapter 2. The Cellular l and Molecular Basis of Cognition Cognitive Neuroscience: The Biology of the Mind, 3 rd Ed., M. S. Gazzaniga, R. B. Ivry, and G. R. Mangun, Norton, 2008. Summarized by B.-W. Ku,

More information

Intro to Cognitive Science

Intro to Cognitive Science Intro to Cognitive Science Jamuna Subramaniam Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur Higher order brain functions Language Learning and memory Thought

More information

Chapter 11: Functional Organization of Nervous Tissue

Chapter 11: Functional Organization of Nervous Tissue Chapter 11: Functional Organization of Nervous Tissue I. Functions of the Nervous System A. List and describe the five major nervous system functions: 1. 2. 3. 4. 5. II. Divisions of the Nervous System

More information

BIOLOGICAL PROCESSES

BIOLOGICAL PROCESSES BIOLOGICAL PROCESSES CHAPTER 3 1 LEARNING GOALS Discuss how the nervous system communicates internally. Describe the structure and function of neurons Describe how the neuron transmits information Describe

More information

What is Anatomy and Physiology?

What is Anatomy and Physiology? Introduction BI 212 BI 213 BI 211 Ecosystems Organs / organ systems Cells Organelles Communities Tissues Molecules Populations Organisms Campbell et al. Figure 1.4 Introduction What is Anatomy and Physiology?

More information

Mossy cells in epilepsy: rigor mortis or vigor mortis?

Mossy cells in epilepsy: rigor mortis or vigor mortis? 140 Opinion Mossy cells in epilepsy: rigor mortis or vigor mortis? Anna d. H. Ratzliff, Vijayalakshmi Santhakumar, Allyson Howard and Ivan Soltesz Mossy cells are bi-directionally connected through a positive

More information

BIOL Week 6. Nervous System. Transmission at Synapses

BIOL Week 6. Nervous System. Transmission at Synapses Collin County Community College BIOL 2401 Week 6 Nervous System 1 Transmission at Synapses Synapses are the site of communication between 2 or more neurons. It mediates the transfer of information and

More information

GABA A Receptors and GABAergic Interneurons in Chronic Temporal Lobe Epilepsy

GABA A Receptors and GABAergic Interneurons in Chronic Temporal Lobe Epilepsy GABA A Receptors and GABAergic Interneurons in Chronic Temporal Lobe Epilepsy December 4, 2010 Carolyn R. Houser Professor, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare

More information

Outline. Neuron Structure. Week 4 - Nervous System. The Nervous System: Neurons and Synapses

Outline. Neuron Structure. Week 4 - Nervous System. The Nervous System: Neurons and Synapses Outline Week 4 - The Nervous System: Neurons and Synapses Neurons Neuron structures Types of neurons Electrical activity of neurons Depolarization, repolarization, hyperpolarization Synapses Release of

More information

*Pathophysiology of. Epilepsy

*Pathophysiology of. Epilepsy *Pathophysiology of Epilepsy *Objectives * At the end of this lecture the students should be able to:- 1.Define Epilepsy 2.Etio-pathology of Epilepsy 3.Types of Epilepsy 4.Role of Genetic in Epilepsy 5.Clinical

More information

Autoimmune epilepsies:

Autoimmune epilepsies: Autoimmune epilepsies: Syndromes and Immunotherapies Sarosh R Irani Associate Professor, Wellcome Trust Intermediate Fellow and Honorary Consultant Neurologist Nuffield Department of Clinical Neurosciences,

More information

ANATOMY AND PHYSIOLOGY OF NEURONS. AP Biology Chapter 48

ANATOMY AND PHYSIOLOGY OF NEURONS. AP Biology Chapter 48 ANATOMY AND PHYSIOLOGY OF NEURONS AP Biology Chapter 48 Objectives Describe the different types of neurons Describe the structure and function of dendrites, axons, a synapse, types of ion channels, and

More information

PSYCH 260 Exam 2. March 2, Answer the questions using the Scantron form. Name:

PSYCH 260 Exam 2. March 2, Answer the questions using the Scantron form. Name: PSYCH 260 Exam 2 March 2, 2017 Answer the questions using the Scantron form. Name: 1 1 Main Please put in their proper order the steps that lead to synaptic communication between neurons. Begin with the

More information

Neural Communication. Central Nervous System Peripheral Nervous System. Communication in the Nervous System. 4 Common Components of a Neuron

Neural Communication. Central Nervous System Peripheral Nervous System. Communication in the Nervous System. 4 Common Components of a Neuron Neural Communication Overview of CNS / PNS Electrical Signaling Chemical Signaling Central Nervous System Peripheral Nervous System Somatic = sensory & motor Autonomic = arousal state Parasympathetic =

More information

CHAPTER 44: Neurons and Nervous Systems

CHAPTER 44: Neurons and Nervous Systems CHAPTER 44: Neurons and Nervous Systems 1. What are the three different types of neurons and what are their functions? a. b. c. 2. Label and list the function of each part of the neuron. 3. How does the

More information

Introduction. 1 person in 20 will have an epileptic seizure at some time in their life

Introduction. 1 person in 20 will have an epileptic seizure at some time in their life Introduction 1 person in 20 will have an epileptic seizure at some time in their life Epilepsy is diagnosed on the basis of two or more epileptic seizures. Around 450,000 people in the UK have epilepsy

More information

INTRODUCTION TO NEUROLOGICAL DISEASE. Learning in Retirement: Epilepsy

INTRODUCTION TO NEUROLOGICAL DISEASE. Learning in Retirement: Epilepsy INTRODUCTION TO NEUROLOGICAL DISEASE Learning in Retirement: Epilepsy Lesson Overview Seizures VS Epilepsy What Causes Seizures? Types of Seizures Epilepsy Pathology General Cellular Molecular Diagnosis

More information

Chapter 11: Nervous System and Nervous Tissue

Chapter 11: Nervous System and Nervous Tissue Chapter 11: Nervous System and Nervous Tissue I. Functions and divisions of the nervous system A. Sensory input: monitor changes in internal and external environment B. Integrations: make decisions about

More information

Nervous Tissue and Neurophysiology

Nervous Tissue and Neurophysiology Nervous Tissue and Neurophysiology Objectives Describe the two major divisions of the nervous system and their characteristics. Identify the structures/functions of a typical neuron. Describe the location

More information

Parahippocampal networks in epileptic ictogenesis

Parahippocampal networks in epileptic ictogenesis Parahippocampal networks in epileptic ictogenesis Marco de Curtis Dept. Experimental Neurophysiology Istituto Nazionale Neurologico Carlo Besta Milano - Italy Amaral, 1999 hippocampus perirhinal ctx entorhinal

More information

All questions below pertain to mandatory material: all slides, and mandatory homework (if any).

All questions below pertain to mandatory material: all slides, and mandatory homework (if any). ECOL 182 Spring 2008 Dr. Ferriere s lectures Lecture 6: Nervous system and brain Quiz Book reference: LIFE-The Science of Biology, 8 th Edition. http://bcs.whfreeman.com/thelifewire8e/ All questions below

More information

Chapter 45: Synapses Transmission of Nerve Impulses Between Neurons. Chad Smurthwaite & Jordan Shellmire

Chapter 45: Synapses Transmission of Nerve Impulses Between Neurons. Chad Smurthwaite & Jordan Shellmire Chapter 45: Synapses Transmission of Nerve Impulses Between Neurons Chad Smurthwaite & Jordan Shellmire The Chemical Synapse The most common type of synapse used for signal transmission in the central

More information

BIOLOGY 2050 LECTURE NOTES ANATOMY & PHYSIOLOGY I (A. IMHOLTZ) FUNDAMENTALS OF THE NERVOUS SYSTEM AND NERVOUS TISSUE P1 OF 5

BIOLOGY 2050 LECTURE NOTES ANATOMY & PHYSIOLOGY I (A. IMHOLTZ) FUNDAMENTALS OF THE NERVOUS SYSTEM AND NERVOUS TISSUE P1 OF 5 P1 OF 5 The nervous system controls/coordinates the activities of cells, tissues, & organs. The endocrine system also plays a role in control/coordination. The nervous system is more dominant. Its mechanisms

More information

Model neurons!!!!synapses!

Model neurons!!!!synapses! Model neurons ynapses uggested reading: Chapter 5.8 in Dayan,. & Abbott, L., Theoretical Neuroscience, MIT ress, 200. Model neurons: ynapse Contents: ynapses ynaptic input into the RC-circuit pike-rate

More information

Action potentials propagate down their axon

Action potentials propagate down their axon Action potentials propagate down their axon Larger diameter axons have less resistance to ion flow Speed of conduction is faster in large diameter axons Saltatory conduction in myelinated axons Large myelinated

More information

FIRST MIDTERM EXAM October 18, 2011 BILD2

FIRST MIDTERM EXAM October 18, 2011 BILD2 FIRST MIDTERM EXAM October 18, 2011 BILD2 WRITE YOUR NAME ON ALL 6 PAGES. ANSWER ALL 10 QUESTIONS (100 POINTS). CONFINE YOUR ANSWERS TO THE SPACE ALLOWED. If you would like to write on the back of the

More information

Synaptic Transmission

Synaptic Transmission Synaptic Transmission Postsynaptic Mechanisms Synapses electrical and chemical Part I Neurotransmitters categories and life cycle Neurotransmitters examples and postsynaptic effects Pathology Part II Neurotransmitter

More information

10.1: Introduction. Cell types in neural tissue: Neurons Neuroglial cells (also known as neuroglia, glia, and glial cells) Dendrites.

10.1: Introduction. Cell types in neural tissue: Neurons Neuroglial cells (also known as neuroglia, glia, and glial cells) Dendrites. 10.1: Introduction Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell types in neural tissue: Neurons Neuroglial cells (also known as neuroglia, glia, and glial

More information

Cellular Bioelectricity

Cellular Bioelectricity ELEC ENG 3BB3: Cellular Bioelectricity Notes for Lecture 24 Thursday, March 6, 2014 8. NEURAL ELECTROPHYSIOLOGY We will look at: Structure of the nervous system Sensory transducers and neurons Neural coding

More information

Physiological and Physical Basis of Functional Brain Imaging 6. EEG/MEG. Kâmil Uludağ, 20. November 2007

Physiological and Physical Basis of Functional Brain Imaging 6. EEG/MEG. Kâmil Uludağ, 20. November 2007 Physiological and Physical Basis of Functional Brain Imaging 6. EEG/MEG Kâmil Uludağ, 20. November 2007 Course schedule 1. Overview 2. fmri (Spin dynamics, Image formation) 3. fmri (physiology) 4. fmri

More information

MECHANISM OF EPILEPSY 1

MECHANISM OF EPILEPSY 1 SHIN MECHANISMS Annu. Rev. & MCNAMARA Med. 1994. OF 45:379 89 EPILEPSY MECHANISM OF EPILEPSY 1 Cheolsu Shin, M.D. Departments of Neurology and Pharmacology, Mayo Foundation, Rochester, Minnesota 55905

More information

What effect would an AChE inhibitor have at the neuromuscular junction?

What effect would an AChE inhibitor have at the neuromuscular junction? CASE 4 A 32-year-old woman presents to her primary care physician s office with difficulty chewing food. She states that when she eats certain foods that require a significant amount of chewing (meat),

More information

Omar Sami. Muhammad Abid. Muhammad khatatbeh

Omar Sami. Muhammad Abid. Muhammad khatatbeh 10 Omar Sami Muhammad Abid Muhammad khatatbeh Let s shock the world In this lecture we are going to cover topics said in previous lectures and then start with the nerve cells (neurons) and the synapses

More information

THE HISTORY OF NEUROSCIENCE

THE HISTORY OF NEUROSCIENCE THE HISTORY OF NEUROSCIENCE BIOLOGICAL ASPECTS OF BEHAVIOR: THE NEURON & NEURAL COMMUNICATION NERVOUS SYSTEM Combined activity of the brain, spinal cord & other nerve fibers Acts as an information processing

More information

Neurobiology: The nerve cell. Principle and task To use a nerve function model to study the following aspects of a nerve cell:

Neurobiology: The nerve cell. Principle and task To use a nerve function model to study the following aspects of a nerve cell: Principle and task To use a nerve function model to study the following aspects of a nerve cell: INTRACELLULAR POTENTIAL AND ACTION POTENTIAL Comparison between low and high threshold levels Comparison

More information

Action Potentials and Synaptic Transmission. BIO 219 Napa Valley College Dr. Adam Ross

Action Potentials and Synaptic Transmission. BIO 219 Napa Valley College Dr. Adam Ross Action Potentials and Synaptic Transmission BIO 219 Napa Valley College Dr. Adam Ross Review of action potentials Nodes of Ranvier Nucleus Dendrites Cell body In saltatory conduction, the nerve impulses

More information

Synaptic Plasticity and Memory

Synaptic Plasticity and Memory Synaptic Plasticity and Memory Properties and synaptic mechanisms underlying the induction of long-term potentiation (LTP) The role of calcium/calmodulin-dependent kinase II (CamKII) in the induction,

More information

NEURAL TISSUE (NEUROPHYSIOLOGY) PART I (A): NEURONS & NEUROGLIA

NEURAL TISSUE (NEUROPHYSIOLOGY) PART I (A): NEURONS & NEUROGLIA PART I (A): NEURONS & NEUROGLIA Neural Tissue Contains 2 kinds of cells: neurons: cells that send and receive signals neuroglia (glial cells): cells that support and protect neurons Neuron Types Sensory

More information

The Nervous System. Dr. ZHANG Xiong Dept. of Physiology ZJU School of Medicine.

The Nervous System. Dr. ZHANG Xiong Dept. of Physiology ZJU School of Medicine. The Nervous System Dr. ZHANG Xiong Dept. of Physiology ZJU School of Medicine Http://10.10.10.151 Part 1. Summary of the nervous system The Nervous System Central Nervous System Brain + Spinal Cord Peripheral

More information

Cellular Neurobiology / BIPN 140

Cellular Neurobiology / BIPN 140 SECOND MIDTERM EXAMINATION Fall, 2015 GENERAL INSTRUCTIONS 1. Please write your name on ALL 6 pages. 2. Please answer each question IN THE SPACE ALLOTTED. 1) /10 pts 2) /10 pts 3) /15 pts 4) /15 pts 5)

More information

Neurons! John A. White Dept. of Bioengineering

Neurons! John A. White Dept. of Bioengineering Neurons! John A. White Dept. of Bioengineering john.white@utah.edu What makes neurons different from cardiomyocytes? Morphological polarity Transport systems Shape and function of action potentials Neuronal

More information

Lecture 3 (Oct 5 th ): NEURONS AND NERVE IMPULSES Lecture Outline

Lecture 3 (Oct 5 th ): NEURONS AND NERVE IMPULSES Lecture Outline Lecture 3 (Oct 5 th ): NEURONS AND NERVE IMPULSES Lecture Outline 1) CNS vs. PNS 2) Structure of Neurons parts of a neuron: soma, dendrites, axons 3) Glial Cells 4) Mitosis and Regeneration in Neurons

More information

BIPN140 Lecture 12: Synaptic Plasticity (II)

BIPN140 Lecture 12: Synaptic Plasticity (II) BIPN140 Lecture 12: Synaptic Plasticity (II) 1. Early v.s. Late LTP 2. Long-Term Depression 3. Molecular Mechanisms of Long-Term Depression: NMDA-R dependent 4. Molecular Mechanisms of Long-Term Depression:

More information