MD2020 Neuroscience

INTRODUCTION TO NEUROTRANSMISSION
Anna Marie Babey Rm 226 BMTVS Bldg Ph. 4781 6992 Email: annamarie.babey@jcu.edu.au

Neurotransmission
location communication = synapse transmitting neuron = presynaptic neuron recipient neuron = post-synaptic cell gap between cells = synaptic cleft drive for transmission = synaptic potential

Neuron-to-Neuron Neurotransmission
Source: Marieb & Hoehn

3 types of synapses: axon onto dendrite axon onto axon axon onto cell body single cell can synapse onto numerous other cells

Source: Squire et al., Fundamental Neuroscience 2nd Ed

Nature of Neurotransmission
direct physiological action
e.g. NMJ = muscle activation, sympathetic synapse at SA node increases HR

link in chain
e.g. incoming sensory neuron in spinal cord, activates ascending sensory pathways headed to thalamus, then connects to all points beyond

modulatory influence
positive or negative influence on transmission of another neuron

Transmitting a Signal
saltatory conduction incoming AP triggers driven by Ca+2 influx through voltagegated Ca+2 channels

synaptic potential

Source: Marieb & Hoehn

mobilises synaptic vesicles to presynaptic membrane

Synaptic Vesicles
Source: Squires, et al. Fundamentals of Neuroscience. 2nd Ed

NT packaged into synaptic vesicles in preparation for release release is quantal fixed number of vesicles released per fixed amount of Ca+2

Neurotransmitters
3 classes:
amines acetylcholine (ACh), noradrenaline (NA), serotonin (5HT) amino acids glutamate, -aminobutyric acid (GABA), glycine, aspartate peptides enkephalins, substance P, neuropeptide Y

Neurotransmitters
classically synthesised in axon terminal & packaged into synaptic vesicles
rate-limiting step activity of an enzyme, substrate availability, etc

BUT peptide transmitters synthesised in cell body & transported to axon terminal (*) packaging demands presence of active transport into vesicles

generally driven by pump such as proton (H+) pump of ACh or NA terminals

Synaptic Vesicles

Note: not all proteins associated with vesicles are shown

Vesicle Mobilisation

Zigmond, et al. Fundamentals of Neuroscience. Academic Press. 1999

in response to Ca+2, tethered vesicles are mobilised to presynaptic membranes

many proteins involved botulinum toxins (e.g. Botox) = enzymes targetting synaptic proteins, particularly ACh synapses

Neurotransmitter Release
vesicle membrane anchored to presynaptic membrane to create release pore
NOTE: dont need to know the names of the proteins, just that they anchor & create pore NTs enter synaptic cleft & passively diffuse to post-synaptic membrane estimated 200-500 vesicles per terminal estimated 1014 to 1015 synapses per mammalian brain
Source: Squires, et al., Fundamental Neuroscience. 2nd Ed

Communication
post-synaptic cell receives NT signal via ligand-selective protein interactions

ligand-gated ion channels ( = ionotropic) e.g. nicotinic acetylcholine receptor channels at NMJ neurotransmitter receptors (= metabotropic) use second messenger-linked process mediated by G proteins linked to either ion channels or enzymes e.g. beta adrenergic receptors of SA node

Signal Termination
intent of neuronal activity = punctuated response not ongoing stimulation therefore quick termination of signal = discrete event 2 methods: synaptic enzyme = destroy NT & stop signalling e.g. acetylcholinesterase (AChE) breaks ACh into acetic acid + choline rapid re-uptake (transport) into one or both of pre-synaptic & post-synaptic cells e.g. uptake 1 protein in NA

Signal Termination
2 fates for NTs taken back up into presynaptic terminals:

recycling NT re-packaged into synaptic vesicles, decreasing de novo synthesis enzymatic degradation NT broken down into metabolites measurement of NT metabolites in CSF = common way to estimate activity of NT pathways

Synaptic Monitoring
pre-synaptic terminal requires way to monitor NT release
express autoreceptors (= eyes of synapse) triggers feedback block of further NT release keeps signalling discrete & punctuated most autoreceptors negatively coupled to adenylate cyclase to decrease cAMP production loss of cAMP closes Ca+2 channels to stop vesicle mobilisation & release

ACh synthesis

An Example

synthesis driven by Presynaptic choline terminal acetyltransferase (send) (CAT)

rate limiting rate-limiting step of step
Autoreceptor

signal termination

ACh synthesis = uptake of choline into terminal by choline carrier

Post-synaptic terminal (receive)

signal termination by acetylcholinesterase (AChE)

Regulation of Receptor Responses

if NT available for more than punctuated, short-term delivery, receptor activity altered as reaction to on-going stimulation
desensitisation reduction in response that NT elicits due to loss of sensitivity of receptor

down-regulation reduction in response to NT based on loss of number of receptors

Regulation of Receptor Responses

if certain NT in specific pathways available for more than punctuated, short-term delivery or if antagonist is administered for more than short-term exposure, receptor activity altered as reaction to on-going stimulation
supersensitivity marked increase in response that NT elicits due to loss of sensitivity of receptor up-regulation increase in response to NT based on increased number of receptors

Neuromodulation
= fine-tuning (volume control) of signal extremely diverse group
NTs from adjacent synapse metabolic products (e.g. adenosine, ATP, H+) hormones (e.g. oestrogen) gases (e.g. nitric oxide, carbon dioxide) etc.

Neuromodulation
some NTs released into extracellular fluid instead of into synaptic cleft
creates broad distribution of signal across brain brain stem, cortex, thalamus, cerebellum, spinal cord causes synchronous activation of disparate region to elicit markedly different response from synaptic activity