Neurons + Neurotransmission

Transmit info via white matter to other regions of the brain
Found in cortex

Where the cell bodies are

Phospholipid bilayer
Fluid lipophilic layer
Ion channels

In axon, p.d. of -70mV (hyperpolarised)
High anion conc inside, low outside
Na+ lower conc. inside, higher outside
K+ higher con. inside, lower outside
Na+ channels closed
Some K+ channels open
Na+/K+ pump moves K+ in and Na+ out

Stimualted shape of axon potential in giant squid axon
Na+/K+ currents used to explain AP

Myelination
Axon diameter

Insulates axon
Causes saltatory conduction
Depolarisation only at nodes of ranvier

Large diamter axons have a lower internal resistance

Excitatory postsynaptic potential
Inhibitory postsynaptic potential

Graded change in potential
When info arrives at dendrites

All-or-none AP
Once info reaches axon

Distance and time of graded potentials

Distance over which voltage decreases by 63%

Time for voltage to increase/decrease by 63%

Temporal summation
Spatial summation

-55mV

Chemical
Electrical

Bidirectional
AP enters presynaptic terminal
Connexons form hemichannels
Depolarised charge moves into post synaptic neuron
Direct coupling process

Axosomatic
Axodendritic
Axo-axonic

Normally inhibitory

Excitatory - further from soma
Inhibitory - nearer soma
Temporal and spatial summation

Decreases release of a neurotransmitter from axon terminals
Pre synaptic inhibition

Temporal
Nasal

Vertical bars (simple)
Moving verticle bars (complex)

Shultz
Reward prediction errors (RPEs)

Firing neuron consistantly and persistently, growth occurs

Action potentials

Plasticity related proteins

Strong activation of neuron 1 leads to formation of PRPs that strengthen synapses associated with a weakly stimulated neuron 2
Rogerson et al 2014

1 presynaptic neuron = high activation
Second presynaptic neuron = low activation
Both synaptic inputs will strengthen - likely a result of the PRPs (diffuse to neighbouring synaoses, binding together the different synaptic inputs)

Na+ in

GABA causes Cl- to enter post synaptic neuron OR K+ to leave neuron
Causes hyperpolarisation

Ionotrophic
Metabotrophic (g-protein-coupled receptors)

Ion channel
Neutransmitter binds directly
Increases conductance of particular ion
Important for fast neurotransmission

Alpha
Beta
Gamma

Dissociates and moves through lipid bilayer

About 5%
Largest family are rhodopsin-like (sensory system)

Signal amplification to increase sensitivity:
G proteins activate a population of effector proteins, each generating second messages, leading to multiple actions (opening ion channels)

Blocking active reuptake
Enzymatic degradation

Excess neurotransmitter absored in synaptic cleft, some neurotransmitter taken up by reuptake transporter [eugh]

Block noradrenaline and serotonin reuptake transporters

True
In most cases

Cholinergic synapse
Acetylcholine (ACh) is the NET
Once released into synape ACh degraded by acetylcholinesterase (AChE)
Choline and acetate then recycled back into presynaptic terminal
AChE blocked by Tracine (treat Alzheimer's disease)

Ach has ionotrophic receptor (nicotinic receptor)
When activated lets through positive charge
Also has a g coupled protein receptor (muscarinic receptor)

Clump of neurons
Creates a cable of axons

Amino acid neurotransmitters

Gamma Amino-Butyric Acid

GABA = inhibitory
Glutamate = excitatory

NMDA receptors

Binds to ionotropic and metabotropic receptors
Actively taken up by transporters in nearby glial cells

Permits / blocks passage through a cell membrane in response to a chemical stimulus

Ligand-gated ionotrophic receptor
At rest = blocked by Mg2+ ions
Gates Na+ and Ca2+ (and K+)
Generates an EPSP (excitatory post synaptic potential)
Involved in synaptic plasticity and memory function

Control movement

Glutamate

Formation of precursor (glutamate)
Synthesis (glutamic acid decarboxylase - responsible for the conversion of glutamate into GABA)
Release by exocytosis
Binding to GABA receptors
Binding to presynaptic receptors
Uptake by glia
Conversion to glutamte and glutamine

GABA-A receptor

Made up of 5 subunits
GABA binding causes Cl- to enter neuron
Hyperpolarising (less likely neuron will reach threshold to produce AP)

Fine tuning of neuronal function

Subset of neurotransmitters that change excitability of a neuron by changing the neuron's cellular and synaptic properties
Slower time scales than neurotransmitters
Normally use metabotropic (G-protein coupled receptors) rather thn ionotropic receptors
Eg. dopamine, serotonin Ach, noradrenaline, neuropeptides

Dopamine
Serotonin
Noradrenaline
(all have amine group)

DAT
Torres et al., 2003

NET
Torres et al., 2003

SERT
Torres et al., 2003

Ventral tegmental area
Substantia nigra

Involved in movement
Degenration of dopamine neurons in substantia nigra leads to Parkinson's disease

Schultz
Showed that through conditioning of a stimulus which predicts the onset of reward, the activity of dopamine neurons will track the most predictive stimulus
Once stimulus is fully predicted, there's no more surprise and activity drops

Dopamine receptor
G-protein coupled receptor (metabotropic)
Expressed in striatum
Low expression of D2 receptors in brain linked to addiction and eating disorders
Taq1A A1 allele, a mutation, leads to reduced D2 receptor expression and function
Ppl with high BMI and A1 allele show reduced activation of striatum (part of reward system) in response to milkshake - Stice et al, 2008

Dopamine and noradrenaline richly innervate (to supply with nerves) prefrontal cortex
Brozoski and Goldman Rakic 1979 - dopamine plays critical role in short term spatial memory
Domapine neurons contribute to maintenance and manipulation of info in working memory

Locus coeruleus

Selective attention - phasic activity associated with focussed attention to target stimuli
Detection of novel and salient stimuli - informs hypothalamus of potentially threatening stimuli, mediating fight/flight response
Memory consolidation - noradrenergic transmission strengthens emotional memories
Cortical arousal - locas coeruleus activity fluctuates with different stages of sleep

Adapt to acute stressors
BUT become sensitised with chronic stress - hyperarousal and pathological anxiety

Raphe nuclei

Mood, appetite, sleep - important regulatory role, SSRIs used to treat depression
Behavioural regulation - low serotonin associated with aggression, impulsivitiy and behavioural disinhibition
Stress - chronic, uncontrollable, unpredicatble stress sensitises serotonin systems

Increased activity of 5-HT neurons
Results in abnormal behaviour and mood

Hariri et al, 2002
Short allele = reduced SERT expression, higher 5-HT, increased anxiety
Showed greater activation of amygdala when looking at angry and afraid faces
Hasn't always been replicated tho - controversial