Types of Neurons

The Neuron

The Cell Membrane

Inside the Neuron

Myelination SchwannOligodendrocyte

Astrocytes

Synaptic Transmission and Cellular Communication

Microelectrodes Holder Glass Pipettes ~1  m tips Pulled using heat Filled with Internal solution. Connected via silver wire to an amplifier. Used to record the membrane potential

Cell Activity A Chemical Process Recorded Electrically Electrical activity secondary to chemical events Electrical activity secondary to chemical events Basic Unit Volt – a potential difference between charges in 2 different places in space Volt – a potential difference between charges in 2 different places in space Thus, no single thing has “voltage” Thus, no single thing has “voltage” e.g., battery voltage is determined by the potential difference between 2 terminals e.g., battery voltage is determined by the potential difference between 2 terminals

Basic Concepts Ions – charged particles Anions – Negatively charged particles (chloride: Cl - ) Cations – Positively charged particles (sodium: Na + ; potassium: K + ) Electrostatic Pressure: attraction and repulsion between ions

Basic Ion Concentrations High Sodium and Chloride outside the cell. High Potassium inside the cell.

Ion Distributions Na/K pump maintains Na and K distributions.

Resting Potential of a Neuron = -70 mV The internal environment of the cell is negatively charged in relation to the outside of the cell Four factors interact to maintain the resting potential Random motion Electrostatic pressure Properties of the cell membrane Sodium potassium pump

Selective Permeability of Membranes Some ions permitted to cross more easily than others Neuronal membranes contain ion channels Protein tubes that span the membrane Protein tubes that span the membrane Some stay open all the time (nongated) Some stay open all the time (nongated) Some open on the occasion of an action potential, causing a change in the permeability of the membrane (gated) Some open on the occasion of an action potential, causing a change in the permeability of the membrane (gated)

Ion Channels Recognize and select among specific ions The distribution of ionic species across the membrane depends on the particular distribution of ion channels in the cell membrane.

EPSPs and IPSPs EPSPs and IPSPs are graded responses That is, they are proportional to the intensity of the signal that elicits them Depolarizing Hyperpolarizing

Decremental Conduction Faster (don’t have energy expense of activating voltage gated channels), but lose signal strength over distance.

Action Potential When cells are sufficiently depolarized, voltage-gated channels open up and sodium rushes in, depolarizing the cell to about +50 mV. The point at which the channels open up is called THRESHOLD and represents an all or none event.

Spatial Summation Spatially separate synapses can exhibit spatial summation.

Temporal Summation Activity from one synapse can exhibit temporal summation.

Components of an Action Potential Once triggered, an action potential occurs and can’t be stopped. For 1-2 ms after an action potential, it is impossible to elicit a 2 nd A.P. This is called the absolute refractory period. The absolute refractory period is followed by the relative refractory period, where it is only possible to elicit an action potential by applying higher than normal stimulation. The neuron is slightly hyperpolarized during the relative refractory period. AP’s are non-decremental Ap’s travel at about 60 m/s AP’s travel more slowly than Post-Synaptic Potentials

Action Potential: Sodium Ion Movement

Saltatory Conduction Fast (signal is carried passively between nodes) Reliable (signal is regenerated at each node)

Anatomy of a Synapse

Exocytosis: Transmitter Release

Synaptic Transmission (simplified version) When an action potential reaches the terminal button, synaptic vesicles release neurotransmitter (NT) into the synaptic cleft NT diffuses across the cleft At least three possible scenarios after this: -NT molecules do not attach to a postsynaptic receptor -NT released in an area with no immediate receptors -NT binds to a receptor site The latter scenario leads to change in the ionic permeability of the postsynaptic membrane Excitatory postsynaptic potential (EPSP) Inhibitory postsynaptic potential (IPSP) Summation of EPSPs and IPSPs Summation of EPSPs and IPSPs is the main principle of interneuronal communication Summation of EPSPs and IPSPs

Ion Channels Ionotropic Metabotropic

Neurotransmitter Deactivation 3 main processes 3 main processes Diffusion: neurotransmitter diffuses away from synapse, reduces amount available for binding, adequate for cases where precise timing not critical, diffusion most often involved in inactivation of peptide neuromodulators. Inactivation by Enzymatic degradation: enzyme degrades neurotransmitter directly. Most common is acetylcholinesterase that degrades acetylcholine; also monoamine oxidase (MAO) and catechol-O-methyl- transferase (COMT) that degrade the monoamines Reuptake: Most common. Neurotransmitter is taken back up into the presynaptic terminal after being released.

7 Steps in Neurotransmission

Classical criterion for neurotransmitter Must be synthesized in the neuron When an action potential occurs it must be released in sufficient quantity to produce an effect on the post-synapatic cell Should be able to experimentally duplicate the action on the post-synapatic cell Some mechanism exists to end the interaction between the chemical and the post-synaptic cell

Hormones Classical definition: Substances that are released from the tissue in which they are synthesized and then travel via blood to other organs whose activities they influence. Actions of hormones tend to be slower and much longer lasting than actions of NTs Neurohormones are also called neuroactive peptides and are synthesized in hypothalamus and transported to pituitary gland that releases them: e.g. oxytocin (regulates smooth muscle contraction), vasopressin (regulates water balance) We now know that neurohormones can be released at the synapse alone or in conjunction with NTs and can produce NT-like effects (i.e. rapid communication)

Neurotransmitters are generally classified according to molecular size Small molecule neurotransmitters Amino acids (glutamate, GABA, aspartate, glycine) Monoamines (dopamine, norepinephrine, epinephrine, serotonin) Soluble gases (nitric acid, carbon monoxide) Acetylcholine (NT at neuromuscular synapses) Large molecule neurotransmitters Peptides

Classes of Neurotransmitters I I (50+) (1) (2) Not released, diffuse through cell walls (4)

Distribution of Neurotransmitters Distribution of Neurotransmitters Acetylcholine (ACh) Acetylcholine (ACh) In the CNS, involved in motor function, attention, learning and memory Serotonin (5-HT) Serotonin (5-HT) Plays a major role in the sleep-wake cycle Low levels associated with severe depression Norepinephrine (NE): Norepinephrine (NE): Involved in mood, memory, motor behavior, depression, and anxiety Dopamine (DA) Dopamine (DA) Crucial to our ability to move efficiently and effectively, implicated in motivation, mood, perception Amino Acids Amino Acids GABA: Most common inhibitory neurotransmitterGABA: Most common inhibitory neurotransmitter Glutamate: Most widespread excitatory neurotransmitterGlutamate: Most widespread excitatory neurotransmitter Glycine: inhibitory NT important in spinal cord and brain stemGlycine: inhibitory NT important in spinal cord and brain stem

Making Catecholamines in 4 easy steps Dopamine Norepinephrine a.k.a Noradrenaline Epinephrine a.k.a Adrenaline Phenylethanolamine N-methyltransferase

Making serotonin Tryptophan Enzyme tryptophan hydroxylase makes 5-hydroxytryptophan Enzyme 5HT decarboxylase makes 5-hydroxytryptamine (5-HT) Monoamine oxidase breaks down 5-HT

GABA Found almost exclusively in brain Glutamic acid Enzyme glutamic acid decarboxylase makes Gamma amino butyric acid (GABA)

Neuropeptides Large molecule NTs Can be released into circulation and act at a distant site, or can be confined to synapse Synthesized at soma and transported to release sites (NTs are synthesized in synaptic terminal) Have slow postsynaptic effects and actions are terminated b y diffusion or extracellular degradation Do not require point to point synaptic connections to produce actions Co-released with classical NTs. Egs: Substance P, Neurotensin, thyrotropin releasing hormone (TRH), oxytocin, vasopressin, met-enkephalin, prolactin