W1L2: Glutamate and GABA - Alcohol, Ketamine, Psychosis and Epilepsy

GABA and glutamate: evolution

believed to be first to evolve and found in simple organisms

GABA and glutamate: common neurotransmitters

most common neurotransmitters in CNS

glutamate: function

main excitatory neurotransmitter in brain (neurotransmitter released by all excitatory neurons), estimated over half of all brain synapses release glutamate

glutamate: percentage of cerebral cortex

80% cerebral cortex consists of pyramidal cells (glutamatergic)

glutamate: synthesis: glutamic acid

amino acid that acts as neurotransmitter in its original form but doesn’t pass blood brain barrier so needs to be synthesised in brain

glutamate: synthesis: glutamine

released from cells neighbouring neurons and causes synthesisation

excitatory neurons: location

found in most of long projection neurons throughout cortex - convey info from sensory organs to brain and vice versa

glutamate: receptors

inotropic (ion channels) and metabotropic (g-protein coupled)

glutamate: receptors: ion channels

NMDA receptor

AMPA receptor

Kainate receptor

glutamate: receptors: g-protein coupled

metabotropic glutamate receptors (mGluR’s)

glutamate: NMDA receptors

has at least 6 different binding sites (lots of complex functions)

glutamate: NMDA receptors: only work if

1. also glycine molecule (another amino acid) attached

   1. if magnesium ion is NOT bound inside

glutamate: NMDA receptors: magnesium ion to pop out

if amber receptor depolarises close to it, changes polarisation and magnesium pops out due to depolarisation

glutamate: NDMA receptors: 6 binding sites

polyamide, glutamate, Zn2+ (zinc), glycine, Mg2+ (magnesium), PCP

glutamate: NMDA: alcohol

NMDA antagonist (blocks glutamatergic functioning which blocks info processing and excitatory functioning) - reduction in glutamate by alcohol contributes to sedative effects and memory effects of alcohol

GABA: NMDA: alcohol

also GABA agonist - increasing inhibition, decreasing excitatory functioning

NDMA receptors: PCP

phencyclidine - angel dust

NDMA receptors: ketamine and PCP

NDMA antagonist that cause dissociative hallucinations, disconnect self from reality, diffuse cortical function, synch with auditory stimulation, sensory anaesthetic

glutamate: ketamine: NDMA binding

Ketamin binds to same place PCP and blocks channel from depolarising

ketamine: depression

effective treatment for individuals resistant to depression drugs (works quickly lasts for a while but people snap back)

glutamate and psychosis

regardless of exact neurotransmitter involvement, symptoms of psychosis suggest widespread disruption and lack of coherent integration of sensor information - no major structural differences in psychosis so illustrates importance of chemical balance in healthy perception and cognition

NDMA: activity critical for

learning, memory, perception and synaptic plasticity

GABA (gamma-amino butyric-acid)

primary inhibitory neurotransmitter (decrease likelihood of post-synaptic neuron firing)

without inhibitory synapses

brain would be unstable with neurone firing uncontrollably (causing seizures)

GABA: neuron size

short local inhibitory neurons - form dense web around and between excitatory neuron

GABA: synthesis

produced from glutamic acid (glutamate is same amino acid) - glutamate is converted into GABA and GABA can be converted to glutamate by enzymes

GABA: receptors

A - ion channels, B- G protein-coupled

GABA agonist (+)

can perform natural inhibitory roles

GABA antagonist (-)

can’t exert natural inhibitory roles

GABA agonists

benzodiazepines, muscimol (psychoactive compounds in mushrooms), barbiturates (anticonvulsants + anaesthetics), alcohols

GABA antagonists

picrotoxin (epileptogenic seizure causing drugs)

seizure disorders

relatively common with 400,000 in Australia

generalised seizures

widespread and involve most of brain

partial seizures

definite focus and restricted to small part of brain (often scarred region caused by injury or developmental abnormality)

seizures and heat

heat can kill neutrons - fevers can cause seizures therefore not vaccines which cause seizure but fevers associated with vaccines