Types of NeuronsTypes of Neurons

The NeuronThe Neuron

The Cell MembraneThe Cell Membrane

Inside the NeuronInside the Neuron

MyelinationMyelination

Schwann Oligodendrocyte

AstrocytesAstrocytes

Synaptic Transmission and Synaptic Transmission and Cellular CommunicationCellular Communication

MicroelectrodesMicroelectrodes

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 ActivityCell Activity

A Chemical ProcessA Chemical ProcessRecorded ElectricallyRecorded Electrically Electrical activity secondary to chemical Electrical activity secondary to chemical

eventsevents

Basic UnitBasic Unit Volt – a potential difference between Volt – a potential difference between

charges in 2 different places in spacecharges 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 e.g., battery voltage is determined by the potential difference between 2 terminalsdifference between 2 terminals

Basic ConceptsBasic ConceptsIons – charged particlesIons – charged particles

Anions – Negatively charged particles (chloride: ClAnions – Negatively charged particles (chloride: Cl--))

Cations – Positively charged particles (sodium: NaCations – Positively charged particles (sodium: Na++; ; potassium: Kpotassium: K++))

Electrostatic Pressure: attraction and repulsion Electrostatic Pressure: attraction and repulsion between ionsbetween ions

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

Ion DistributionsIon Distributions

•Na/K pump maintainsNa 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 motionElectrostatic pressure

Properties of the cell membraneSodium potassium pump

Selective Permeability of Selective Permeability of MembranesMembranes

Some ions permitted to cross more easily Some ions permitted to cross more easily than othersthan others

Neuronal membranes contain ion Neuronal membranes contain ion channelschannels Protein tubes that span the membraneProtein 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 Some open on the occasion of an action

potential, causing a change in the permeability potential, causing a change in the permeability of the membrane (gated)of the membrane (gated)

Ion ChannelsIon Channels

Recognize and select among specific ionsRecognize and select among specific ions

The distribution of ionic species across The distribution of ionic species across the membrane depends on the particular the membrane depends on the particular distribution of ion channels in the cell distribution of ion channels in the cell membrane.membrane.

EPSPs and IPSPsEPSPs and IPSPsEPSPs and IPSPs are graded responses

That is, they are proportional to the intensity of the signal that elicits them

Depolarizing

Hyperpolarizing

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

Action PotentialAction PotentialWhen 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 SummationSpatial SummationSpatially separate synapses can exhibit spatial summation.

Temporal SummationTemporal Summation

Activity from one synapse can exhibit temporal summation.

Components of an Action PotentialComponents of an Action PotentialOnce triggered, an action potential occurs and can’t be stopped. For 1-2 ms after an action potential, it is impossible to elicit a 2nd 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-decrementalAp’s travel at about 60 m/sAP’s travel more slowly than Post-Synaptic Potentials

Action Potential: Sodium Ion MovementAction Potential: Sodium Ion Movement

Saltatory ConductionSaltatory ConductionFast (signal is carried passively between nodes)Reliable (signal is regenerated at each node)

Figure 5.3, Bear, 2001

EM of Chemical synapse

Active Zone

mitochondria

Anatomy of a SynapseAnatomy of a Synapse

Figure 4-18b, Sherwood, 2001

Anatomy of a SynapseAnatomy of a Synapse

Exocytosis: Transmitter ReleaseExocytosis: Transmitter Release

Synaptic Transmission (simplified version)Synaptic Transmission (simplified version)When an action potential reaches the terminal button, When an action potential reaches the terminal button,

synaptic vesicles release neurotransmitter (NT) into synaptic vesicles release neurotransmitter (NT) into the synaptic cleftthe synaptic cleft

NT diffuses across the cleftNT diffuses across the cleftAt least three possible scenarios after this:At least three possible scenarios after this:

-NT molecules do not attach to a postsynaptic -NT molecules do not attach to a postsynaptic receptorreceptor

-NT released in an area with no immediate -NT released in an area with no immediate receptorsreceptors

-NT binds to a receptor site -NT binds to a receptor site The latter scenario leads to change in the ionic The latter scenario leads to change in the ionic

permeability of the postsynaptic membranepermeability of the postsynaptic membraneExcitatory postsynaptic potential (EPSP)Excitatory postsynaptic potential (EPSP)Inhibitory postsynaptic potential (IPSP)Inhibitory postsynaptic potential (IPSP)

Summation of EPSPs and IPSPs is the main principle is the main principle of interneuronal communicationof interneuronal communication

Ion ChannelsIon Channels

Ionotropic

Metabotropic

Neurotransmitter DeactivationNeurotransmitter Deactivation

3 main processes3 main processes

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

7 Steps in Neurotransmission7 Steps in Neurotransmission

Classical criterion for neurotransmitterClassical criterion for neurotransmitter

Must be synthesized in the neuronMust be synthesized in the neuronWhen an action potential occurs it must be When an action potential occurs it must be released in sufficient quantity to produce an released in sufficient quantity to produce an effect on the post-synapatic celleffect on the post-synapatic cellShould be able to experimentally duplicate the Should be able to experimentally duplicate the action on the post-synapatic cellaction on the post-synapatic cellSome mechanism exists to end the interaction Some mechanism exists to end the interaction between the chemical and the post-synaptic cellbetween the chemical and the post-synaptic cell

HormonesHormones

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

Neurotransmitters are generally classified Neurotransmitters are generally classified according to molecular sizeaccording 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 NeurotransmittersClasses of Neurotransmitters

I

I(50+)

(1)

(2)Not released, diffuse through cell walls

(4)

(4)

Distribution of NeurotransmittersDistribution of Neurotransmitters• AcetylcholineAcetylcholine (ACh) (ACh)

In the CNS, involved in motor function, attention, learning and In the CNS, involved in motor function, attention, learning and memorymemory

• SerotoninSerotonin (5-HT) (5-HT)Plays a major role in the sleep-wake cyclePlays a major role in the sleep-wake cycleLow levels associated with severe depressionLow levels associated with severe depression

• NorepinephrineNorepinephrine (NE): (NE):Involved in mood, memory, motor behavior, depression, and Involved in mood, memory, motor behavior, depression, and anxietyanxiety

• DopamineDopamine (DA) (DA)Crucial to our ability to move efficiently and effectively, Crucial to our ability to move efficiently and effectively, implicated in motivation, mood, perceptionimplicated in motivation, mood, perception

• Amino AcidsAmino 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 stepsMaking Catecholamines in 4 easy steps

Dopamine

Norepinephrinea.k.a Noradrenaline

Epinephrinea.k.a Adrenaline

Phenylethanolamine N-methyltransferase

Making serotoninMaking serotonin

TryptophanTryptophan

Enzyme tryptophan hydroxylase makesEnzyme tryptophan hydroxylase makes

5-hydroxytryptophan5-hydroxytryptophan

Enzyme 5HT decarboxylase makesEnzyme 5HT decarboxylase makes

5-hydroxytryptamine (5-HT)5-hydroxytryptamine (5-HT)

Monoamine oxidase breaks down 5-HTMonoamine oxidase breaks down 5-HT

GABAGABA

Found almost exclusively in brainFound almost exclusively in brain

Glutamic acidGlutamic acid

Enzyme glutamic acid decarboxylase Enzyme glutamic acid decarboxylase makesmakes

Gamma amino butyric acid (GABA)Gamma amino butyric acid (GABA)

NeuropeptidesNeuropeptides

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