Synaptic Transmission

electrical synapses

• direct current transfer through membrane junctions btwn cells

• highly localized communication

chemical synapses

• axon releases neurotransmitter into synaptic cleft where it diffuses across and activates receptors on postsynaptic cell

• primary most of synaptic communication among mammalian nervous system

Synaptic Vesicles

involved in storing & releasing neurotransmitters at presyn. terminal

Active Zone

specialized presyn region associated with sun vesicles that release neurotransmitters

postsynaptic density

concentrated area of receptors & proteins on the receiving side

SNARE proteins

catalyze fusion of synaptic vesicles with presyn membrane

Synaptotagmin

Binds Ca and triggers vesicle exocytosis

Where are Ca2+ channels located in relation to release?

• close to release machinery ~20nm

• allows for rapid neuro release

Calcium & Neurotransmitter release

• AP reaches the axon terminal causes opens the voltage gated Ca channels

• Ca enters presyn terminal

• synaptotagmin detects Ca and triggers synaptic vesicle exocytosis

• vesicle fuses with presyn membrane and releases neurotransmitter into synaptic cleft

Neurotransmitter Clearance

• neurotransmitters must be cleared from synaptic cleft so that signaling does not continue indefinitely

• Mechanisms: Reuptake & Breakdown

  • some drugs inhibit reuptake (clears from synapse):

    • SSRIS (inhibit serotonin reuptake prolong serotonergic signaling)

    • Cocaine (inhibit dopamine reuptake)
      
      

Neurotransmitter Receptors

• presynaptic axon releases a neurotransmitter, while postsynaptic neuron expresses receptors for the neurotransmitter

• a single neurotransmitter can act through multiple receptor subtypes

• different receptor subtypes produce different postsynaptic responses

*the effect of a neurotransmitter depends on the neurotransmitter released & the receptors type present on the postsynaptic cell*

Excitatory synaptic transmission

increases excitability of the postsynaptic neuron

Inhibitory synaptic transmission

decrease excitability of postsynaptic neuron

ionotropic receptors

• neurotransmitter gated ion channels

• Neurotransmitter binding directly gates the ion channel

• produce fast synaptic responses

• have a reversal potential & current voltage relationship

• the receptors conductance, difference btwn Vm & reversal potential determine current

Metabotropic Receptors

• G protein coupled receptors

• do not directly form the ion channel through which immediate current flows; indirectly affect other ion channels *activate or inactive them

• slower responses

• can have long lasting and widespread cellular effects

• can produce signal amplification and involve second messenger pathways

Glutamate

• primary excitatory neurotransmitter in the brain

GABA

• primary inhibitory In the brain

Glutamatergic Receptors

• Glutamatergic Ionotropic receptors (fast, direct, excitatory)

  • AMPA, Kainate, NMDA

• metabotropic Glutamate receptors (slow, indirect)

  • divided into groups I, II, III

  • GABA Ionotropic = GABAA

  • GABA Metabotropic = GABAB

AMPA Receptors

• are inotropic receptors, so glutamate binding directly opens recpetor ion channels

NMDA receptors

• unusual bc Mg2 blocks the receptor @ hyperpolarized membrane potentials, as postsyn. membrane depolarizes, Mg@ block is reduced or removed

• requires both presynaptic glutamate release & postsynaptic depolar

  • makes it important detectors of coincident presyn & postsyn activity

GABA A Receptors

• ~70 mV at resting membrane potential

• at resting, driving force close to zero, GABA A current close to zero but can still inhibit neurons through shunting inhibition

• are ionotropic receptors with multiple subunits permeable to anions

Hyperpolarizing inhibition

• occurs when the inhibitory reversal potential is more negative than the resting potential (inside is more neg → resting = -70, Inhib = -80)

  • moves membrane further from AP threshold → probability of firing an AP is reduced

Shunting Inhibition

• inhibitory conductance leaks away excitatory cells making it harder to reach threshold to fire AP (neg inside)

• GABA can inhibit even when current rest is zero

• opening GABA A conductance acts as membrane leak & reduces effect of excitatory inputs

• Division of excitatory inputs by inhibitory inputs

• both hyper polar & shunting reduce prob that the neuron reached AP threshold

*ultimately a leak that in the membrane that reduced excitatory

Synaptic Integration

• neurons process info by integrating synaptic inputs in time & space

• cortical inputs receive ~30,000 inputs

• adds up all the inputs

Temporal Summation

multiple inputs occurring at the same synapse over time can add together

Spatial summation

inputs arriving at different synapses can combine

How does the membrane time constant affect temporal summation?

a larger time constant allows a neuron to integrate inputs over a longer time window

How does distance of an input affect spatial summation?

the distance of a synaptic input from the cell body & neurons membrane properties affect how well spatial inputs are integrated