Lecture 4: Synaptic Transmission, Neurotransmitters, and Receptors

bipolar

neuron structural type

one dendrite, one axon

• goes opposite direction in the body

• Ex. retina, etc

multipolar

neuron structural type

motor neurons and interneurons

• most common type in CNS

unipolar

neuron structural type

psuedounidpolar

• peripheral and central nervous branches (off a single process)

• peripheral NS is sensory

Name the neuron structural type indicated by 1, 2, and 3.

bipolar

multipolar

unipolar

What are the two types of synapses?

electrical and chemical

In an electrical synapse, the current flows between cells via the __________.

gap junctions

Electrical synapse occurs in what types of tissues? are the faster or slower than a chemical synapse?

cardiac and smooth mm.

faster communication and conductivity than a chemical synapse

In a chemical synapse, the current flows between cells via the _________.

synaptic cleft

3 steps of a chemical synapse

1. an AP in the presynaptic cells causes the opening of VGCCs on the membrane

2. Ca2+ influx causes the release of neurotransmitter from the presynaptic terminal (into synaptic cleft)

3. neurotransmitter binds receptors on the postsynaptic membrane

• can lead to either hyper- or depolarization depending on whether it is excitatory or inhibitory (can be both)

Neurons are arranged in circuits where _______ cells synapse on _____ cells.

input

output

Neurons are arranged in circuits where input cells synapse on output cells. The output cell may or may not fire an _______ depending on the amount of __________ provided by the input cells.

action potential

excitation

Types of synaptic arrangements

one-to-one synapses

one-to-many synapses

many-to-many synapses

one-to-one synapses

• neuromuscular junction

• single AP in motoneuron causes a single AP in muscle fiber

• neuromuscular junction

• single AP in motoneuron causes a single AP in muscle fiber

This describes which synaptic arrangement between neurons?

one-to-one synapses

one-to-many synapses

• found in some motoneurons of the spinal cord

• one presynaptic neuron synapses with multiple postsynaptic neurons

• inputs can be excitatory or inhibitory

• found in some motoneurons of the spinal cord

• one presynaptic neuron synapses with multiple postsynaptic neurons

• inputs can be excitatory or inhibitory

This describes which synaptic arrangement between neurons?

one-to-many synapses

many-to-many synapses

• sum of inputs determines whether depolarization is enough to generate an action potential

• many presynaptic cells converge on a postsynaptic cell

• common

• most neurons integrate thousands of excitatory and inhibitory inputs before firing

• sum of inputs determines whether depolarization is enough to generate an action potential

• many presynaptic cells converge on a postsynaptic cell

• common

• most neurons integrate thousands of excitatory and inhibitory inputs before firing

This describes which synaptic arrangement between neurons?

many-to-many synapses

excitatory postsynaptic potentials (EPSPs)

• presynaptic neuron depolarizes postsynaptic neuron, brings neuron’s membrane potential to threshold, and opens NA and K channels

• major excitatory NTS;

  • glutamate (CNS)

  • acetylcholine (NMJ)

What is the major excitatory NT for an excitatory postsynaptic potential in the NMJ? CNS?

acetylcholine

glutamate

inhibitory postsynaptic potentials (IPSPs)

• presynaptic neuron hyperpolarizes postsynaptic neuron, membrane potential moves away from threshold, opens Cl channels

• major inhibitory NTs;

  • GABA

  • glycine

What are the major NTs of inhibitory postsynaptic potentials?

GABA and glycine

Many neurotransmitters can be excitatory or inhibitory depending on the receptor _______.

subtype

spatial summation

• two EPSPs arrive at the postsynaptic cell simultaneously

  • the depolarizations summate

temporal summation

• two inputs arrive at postsynaptic cell in rapid succession

• if they are both inhibitory or excitatory, they will summate

synaptic fatigue

repeated stimulation yields a smaller than expected response

An excitatory stimulus → ____________ → Na+ _______

depolarization

influx

ionotropic receptors

• ligand-gated ion channels that usually open in response to the binding of a NT

• usually located along dendrites or cell bodies and recieve incoming information form other neurons

effects of ionotropic receptors on the psotsynaptic neuron

• may be excited due to Na+ influx → depolarization

• may be inhibited due to K+ efflux or Cl- influx (negative charge in cell) → hyperpolarization

  • Ca2+ influx can contribute to depolarization, but primarily acts in activation of intracellular signalingW

hat are the NTs that activate ionotropic receptors?

glutamate

acetylcholine

GABA

Glycine

Glutamate

• NT that activates ionotropic receptors

• amino acid

• primary excitatory NT in CNS

• AMPA and NMDA receptors

Types of glutamate receptors

AMPA

NMDA

AMPA receptors

• glutamate receptor

• causes depolarization when receptor opens

  • allows Na+ influx and K+ efflux

  • gradient caused by Na+ is higher → positive charge in cell → depolarization

NMDA receptors

• glutamate receptor

• needs both glutamate to bind and a voltage change

• Mg block on channel is removed

• important for learning and memory centers in the brain

acetylcholine

• activate ionotropic receptors

• neurotransmitter used at all vertebrate NMJs

• also used by ANS (PSNS and SNS)

Glycine and GABA

• NT that activates ionotropic receptors

• both AA

• both used in CNS and both bind to chloride channels

• binding of these causes inhibition (an increase of Cl- permeability is inhibitory)

  • GABA_A receptor is associated with chloride

metabotropic receptors

• type of NT receptors

• located along dendrites or cell bodies and recieve incoming information

• slower onset, but longer lasting effects compared to ionotropic receptors

• can use GPCRs

G-protein-coupled receptors (GPCR)

• G-protein activated when neurotransmitter binds to receptor

• G-protein alpha subunit binds GTP

• Beta subunit may activate an ion channel (K+) - direct G-protein gating

  • alpha subunit may activate enzymes that promote second messenger synthesis

The alpha subunit of a GPCR may activate enzymes that promote second messenger synthesis. What are those enzymes, and what second messengers would they promote?

phospholipase C

• IP3 and DAG

adenylyl cyclase

• cAMP

second messengers will activate a protein kinase to give the desired effect in the cell

What NTs activate GPCRs?

• norepinephrine

• glutamate (metabotropic receptor)

• GABA (GABA_B receptor)

norepinephrine (NE)

• activates GPCRs

• uses alpha- or beta-adrenergic receptors

  • B, a1, a2

Beta-adrenergic GPCRs

• NEpi binds

• couple to a stimulatory G-protein subunit → activates cAMP second messenger system

alpha-1 adrenergic receptors

• NEpi binds

• couple to G-protein G_q → activates the phospholipase C second messenger system

alpha-1 adrenergic receptors

• NEpi binds

• couple to an inhibitory G-protein → suppresses cAMP system

glutamate (metabotropic receptor)

• NT that activates GPCRs

• acts on postsynaptic sites in CNS

• modulates cell excitability and synaptic transmission via second messenger pathways

• 3 groups of receptors

  • 1, 2, and 3

group 1 glutamate metabotropic receptors

• increase neuron excitability

• activates phospholipase C pathway

groups 2 and 3 glutamate metabotropic receptors

• suppress neuron excitability

• inhibit adenylyl cyclase pathway

GABA (GABA_B receptor)

• NT that activates GPCRs

• found in CNS and autonomic division of peripheral NS

• GAGA acting via G-proteins linked to K+ channels → hyperpolarize cell at the end of an AP

biogenic amines

norepinephrine (NE)

epinephrine (Epi)

dopamine (DA)

serotonin (5-HT)

histamine

amino acid NTs

glutamate

glycine

gamma-aminobutyric acid (GABA)

NT biochemical property groups (4)

acetylcholine

biogenic amines

amino acid NTs

neuropeptides

neuropeptides

• NTs

• synthesized and packaged in nerve cell body instead of axon terminal

• includes neuromodulators and neurohormones

neuromodulators

• VIP, substance P

• subgroup of neuropeptides

• may act on presynaptic cell to alter amount of NT released

• may be co-secreted with NT to alter response of postsynaptic cell

neurohormones

• subgroup of neuropeptides

• released from neurons into blood

Compare and contrast the speed, duration, receptor, mechanism, and examples of ionotropic and metabotropic receptors.

ionotropic

• speed: fast

• duration: short

• receptor: ion channel

• Mechanism: ion movement

• Example: nicotinic ACh

metabotropic

• speed: slow

• duration: long

• receptor: GPCR

• Mechanism: second messenger

• Example: muscarinic ACh

Most synapses in the NS are _______ synapses, where NTs carry information across a ____________.

chemical

synaptic cleft

__________ alter neuronal communication by modifying neutotransmitter release or the responsiveness of target cells.

Neuromodulators