NEURAL BASES OF LEARNING AND MEMORY. Arlo Clark-Foos
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1 NEURAL BASES OF LEARNING AND MEMORY Arlo Clark-Foos
2 You re Making Me Nervous.System Egyptian and Greek views of the brain Behavioral Research vs. Brain Research
3 Ye Olde Hindbrain Cerebellum, Pons, Medulla Circulation, Respiration, Arousal/Sleep Fine coordination of movement (e.g., eye blink from air puff)
4 Midbrain Tectum, tegmentum Coordinating hearing/vision with movement Orienting and reflexive behaviors (e.g., freezing)
5 More Evolved Forebrain Thalamus, Hypothalamus, Pituitary Gland, Cerebral Cortex (Striatum, Hippocampus, Amygdala)
6 The Cerebral Cortex Front Peak Out Back Cortex (Latin) means Temples 1. Contralateral 2. Distinctions among functions within hemispheres 3. Type of representation Brain stem Cerebellum
7 Cerebral Cortex Contralateral organization
8 Cerebral Cortex Distinctions among functions within hemispheres Primary, Secondary, and Association areas
9 Cerebral Cortex Type of representation (e.g., topographic) More on this later. Yay, brains!
10 Below the Cortex (Subcortical) A society of experts Planning and Producing Skilled Movement synaesthesia Gateway of Sensory Input Emotion Semantic and Episodic Memory
11 Comparative Neuroanatomy In a battle between the cerebellum and cortex, which determines Intelligence? Frogs < Humans < Elephants? Vertebrates (CNS and PNS) vs. Invertebrates (PNS) Human 100 billion Nematode = 302 Octopus > 100 million
12 NEURONS
13 Neurobiology Primer Cell Neuron Circuit System Reticular Theory of Brain Circuitry: fixed wires /sites/cajalbbp2.cesvima.upm. es/files/ramon-y-cajal2.jpg Santiago Ramón y Cajal and the imperfect black reaction Identified functional components of neurons (axon, dendrite, cell body) Neuron Doctrine, directionality Cross-Species Comparisons Nobel Prize with Golgi in 1906
14 Structure of a Neuron Dendrites Receive Signals New Vocabulary Cell Body (Soma) Integrates signals, cellular metabolism Axon(s) Transmits signals (neurotransmitters & vesicles) Pyramidal, Stellate, Interneurons Shapes and functions of neurons. Astrocytes Nutrient & Oxygen Transport Oligodendrocytes Fatty myelin sheath (Multiple Sclerosis)
15 Different Flavors of Neuron (Ramón y Cajal)
16 Neural Communication Synaptic Potentials Action Potential Neurotransmitters (and vesicles) Synapse/Synaptic Cleft
17 Neural Communication 1. Resting Potential (~ -70mV) 2. Synaptic activity, Na+ flows into cell 3. Action potential (~ +40mV) 4. Ca++ flows in, binds vesicles to membrane Neurotransmitter released: 1. If neurotransmitter is excitatory, Na+ will flow into new cell. Excitatory Postsynaptic Potential (EPSP) 2. If neurotransmitter is inhibitory, Cl- will flow into new cell. Inhibitory Postsynaptic Potential (IPSP) 5. Unbinding and recycling neurotransmitter
18 BRAIN STRUCTURE
19 Franz Joseph Gall ( ) Influenced by varying mental capacities 27 different organs in the brain: Organology (phrenology) destructiveness, carnivorous instinct, or tendency to murder
20 Structural Neuroimaging Magnetic Resonance Imaging (MRI) Density and Magnets Slices Diffusion Tensor Imaging (DTI) Type of MRI Water Groups of Axons (White Matter)
21 How does learning affect neurons? Chemical staining (dyeing) Enriched environments More and longer dendrites, more connections London Taxi Cab Drivers (Maguire et al, 2000) and Concert Violinists (Elber et al, 1995)?
22 FUNCTIONAL PROPERTIES
23 Are all behaviors learned? Reflexes Newborns: Sucking, Diving, Palmar Grasp Adults: Knee-jerk, Eyeblink
24 Reflex Arcs Bell-Magendie Law of Neural Specialization (Bell, 1811, Magendie, 1822) Entering Dorsal (sensory/afferent) and Existing Ventral (motor/efferent) Reciprocal Innervation (Sherrington, 1906) Nobel Prize in 1932
25 Incoming Sensory and Outgoing Motor Pathways
26 Otto Loewi ( ) Nobel Prize in 1936 for discovering that chemical (as opposed to electrical) processes controlled neural communication. acetylcholine noradrenaline
27 Electrochemical Control of Behavior Neurotransmitters Refractory Period Inactivation Reputake
28 Functional Neuroimaging & EEG Functional Baseline & Difference Images functional Magnetic Resonance Imaging (fmri) Oxygen (BOLD Signal) New Image every few seconds High Spatial, Moderate Temporal Precision Positron Emission Tomography (PET) Glucose & Positrons New Image every few minutes Moderate Spatial, Low Temporal Precision Electroencephalography (EEG) Constant recording of electrical changes Event-related potential (ERP) Low Spatial, High Temporal Precision
29 Recording Directly From Neurons Single-cell Recording Spikes Georgopolulos et al., 1993
30 PLAYING WITH BRAINS
31 Neuropsychology Aliens, cars, and brains new phrenology Brain Injuries (case studies) & Animal models Karl Lashley s search for engrams Equipotentiality (Flourens, 1824) and the Percentage of our Brains we actually use Learning simply is not possible (Lashley, 1929) Are memories more cortical or subcortical?
32 Homonculus, little man Pavlov s anesthetized dogs (1927) Electrical stimulation Motor Cortex (M1) Fine motor control requires more neurons for specialization Déjà vu and Virtual Reality Training Remembering by the Seat of your Pants Violins and Deep Brain Stimulation
33 Transcranial Stimulation Transcranial Magnetic Stimulation (TMS) Transcranial Direct-Current Stimulation (tdcs) May improve memory disorders (e.g., Floel, 2014)
34 Better Living Through Chemistry Drugs Synaptic Transmission Presynaptic effects e.g., Amphetamines and dopamine, MDMA and serotonin Postsynaptic Receptors e.g., Opiates mimic endogenous opiods (pleasure) Inactivation and Reuptake e.g., Selective serotonin reuptake inhibitors (SSRI; anti-depressants) Cocaine blocks reuptake of dopamine and norepinephrine Ritalin, Adderall, Provigil?
35 Changing Neural Connections Synaptic Plasticity Affecting Connections (Santiago Ramón y Cajal, William James) Donald. O. Hebb, neurons that fire together, wire together Distorted forms and Graceful degradation
36 Long-Term Potentiation and Depression Terje Lømo (Bliss & Lømo, 1973) Changes can last hours
37 Molecular Basis for Associative LTP 1. Synaptic activity in hippocampus releases GLUTAMATE (excitatory) and Ca++ NMDA (blocked by Mg++) AMPA (open) 2. AMPA allows in Na+ 3. Excitatory Postsynaptic Potential (EPSP)
38 Molecular Basis for Associative LTP 4. Activation of postsynaptic dendrite releases Mg++ from NMDA receptors 5. Glutamate binds with NMDA receptor
39 Molecular Basis for Associative LTP 6. NMDA pumps Ca++ into cell Causes AP faster than Na+ 7. Ca++ used to synthesize neurotrophins. 8. Neurotrophins affect synapse (more, larger, stronger connections)
40 Another Graphic of LTP
41 LTP and Memory Evidence from chemical antagonists (Steele & Morris, 1999) e.g., AP5 selectively blocks NMDA receptors
42 How About Improving LTP? Joe Tsien (Tang et al., 1999) and colleagues bred mice with extra NMDA receptors. (Doogie mice)
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