Bioscience in the 21st century

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Bioscience in the 21st century Neurons, Synapses, and Signaling Dr. Michael Burger

Outline: 1. Why neuroscience? 2. The neuron 3. Action potentials 4. Synapses 5. Organization of the nervous system 6. Clinical approaches of today and tomorrow

Alzheimer s Disease more than 5 million people in the United States living with Alzheimer s. The direct and indirect costs of Alzheimer s and other dementias amount to more than $148 billion annually. Parkinson s disease: 3% of population over 65: 1.5 million patients Hearing Impairment: Approximately 28 million Americans have a hearing impairment Approximately 314 in 1,000 people over age 65 have hearing loss and 40 to 50 percent of people 75 and older have a hearing loss. Paralysis: 2.4 million Americans are paralyzed Depression: over 20 million Americans suffer from depression

Figure-ground illusions are well known for visual stimuli

The Müller-Lyer Illusion

The Müller-Lyer Illusion http://www.michaelbach.de/ot/ szemuelue/index.html

http://www.ritsumei.ac.jp/~akitaoka/index-e.html

What did he say?

What did he say? http://www.media.uio.no/personer/arntm/english.html

Now close your eyes!

Hearing gaps

But they occur in the auditory system too!

The BIG THREE topics for today: 1. What is the basis of electrical signaling in neurons? 1I. How do neurons talk to each other? I1I. How do neurons encode information?

The neuron is the unit of processing for the nervous system synapse (glia)

The cell membrane is a phospholipid bilayer nucleus plasma membrane

Cell membranes store Voltage Outside: Extracellular Positive Inside: Cytoplasmic Vmembrane= -60 mv Negative **The inside of the cell is usually more negative than the outside by about -60 mv

This resting voltage depends on ion distribution, and ions in general cannot cross the membrane Extracellular Na K Cl- Ca Cytoplasmic Na K An - (organic anions; ie proteins)

The cell membrane contains proteins, some of which are channels for charged particles

Two (of many) membrane protein types: Ligand gated (chemically gated) Voltage gated

How does an electrical signal occur in a neuron? Na Extracellular Na channel Cytoplasmic K K channel FIRST, WE GIVE THE Na CHANNEL A STIMULUS

Na Extracellular Cytoplasmic K

Na Extracellular Cytoplasmic K

Na Extracellular Cytoplasmic K Voltage

Na Extracellular Voltage gated K channel Cytoplasmic K Voltage

Extracellular -60mV Na Membrane Voltage Cytoplasmic K Voltage Voltage

One more detail... The voltage change travels...

Na The basis of propagation... Voltage K

Action Potential Summary: 2 direction of travel 1 3 Membrane Voltage 1. Na channels open/na flows into the cell 2. Na channels close while K channels are opening 3. K flow out of the cell dominates

NEXT: How do neurons talk to each other?

Synaptic Transmission 1 2 Ca axon terminal axon vesicle transmitter postsynaptic receptor dendrite Step 1: Depolarization of the axon terminal Step 2: Voltage dependent Ca entry

Synaptic Transmission Ca 4 3 Step 3: Ca dependent vesicle fusion Step 4: transmitter release

Synaptic Transmission Ca Na 5 6 Step 5: Activation of ligand gated channel Step 6: Na flux/dendrite depolarization

Synaptic Transmission Ca Na 5 6 7 Step 5: Activation of ligand gated channel Step 6: Na flux/dendrite depolarization Step 7: Action Potential is regenerated postsynaptically

Very large auditory synapse

Stain in red marks postsynaptic receptors

Evaluating Neural responses Action Potential Electrode Amplifier Presynaptic neuron Postsynaptic neuron

AND Finally,... How do neurons encode information? there are two simple ways...

with action potential TIMING... no sound evoked 100 ms tone

...and Neurons signal by changing their firing rate Intensity (db SPL) 10 Louder 20 30 40 50 60 70 100 ms tone 100 ms tone

Spike Rate increases with Intensity Spike Rate Stimulus Intensity

What we learned today: 1. Neurons and glia: characteristics and function 2. Ionic basis of electrical signaling 3. Basics of chemical synaptic signaling 4. How neural activity is recorded 5. How neural activity relates to information processing

Next time... Brain organization New technology for therapy