Cell to Cell Communication

Contract when Ach is released at neuromuscular junction Relax when the alpha-motor neurone itself is inhibited as skeletal muscle fibres only receive one input directly (Ach)

• Larger axon diameter - More myelinated axon

• LOSS of MYELIN • Plaques occur anywhere in CNS white matter • Slows, delays or blocks AP transmission • producing sensory, motor, cognitive or behavioural deficits

• Electrical • -> cardiac function (gap junctions), present in NS, unclear role • Chemical • -> majority, many roles using many NTs, therapeutically VERY relevant

• Synthesis • Release • Action • Removal

• Synthesis in the cell body (eg. neuropeptides) • Local synthesis (eg. catecholamines) (tyr -> l-dopa -> dopamine, NA) eg. Parkinson’s - L-DOPA enzyme increased to produce more dopamine (dopamine involved in mood, memory, movement, attention etc)

• action potential arrives at terminal bouton • activates VGCCs • no calcium inside cell, high outside cell so Ca INFLUX • Calcium binds to vSNARE + tSNARE proteins • triggers fusion, exocytosis eg. Botulinum toxin blocks neuromuscular transmission by interfering with Calcium release

1) excitatory or inhibitory 2) fast (ligand gated/iono) or slow (g protein/metabo)

• glutamate in CNS • Ach @ NMJ • bind to receptor, cause SODIUM influx -> depolarisation -> EPSP (electrotonic)

• GABA • glycine (spinal cord, retina) • bind to receptor, cause CHLORIDE influx -> hyperpolarisation -> IPSP (electrotonic)

• dopamine, ACh, serotonin, NA - long lasting, involve second messengers, used in MODULATORY pathways

• Some drugs bind to same site as NT • –> nicotine at ionotropic nicotinic Ach receptors • –> curare blocks neuromuscular Ach receptors • Some drugs bind to other sites on receptor, to modify response to NT • –> benzodiazepines enhance effect of GABA at GABA receptors • –> strychnine reduces effect of glycine at glycine receptors

1) DIFFUSION - peptides 2) ENYMATIC degradation - AChE (inhibitors of this will inc cholinergic transmission) 3) RE-UPTAKE - dopamine, NA, serotonin 4) GLIAL UPTAKE - glutamate, GABA (by astrocytes - for fast transmitters)

Blocks re-uptake of dopamine into pre-synaptic membrane, resulting in a greater ‘reward’ feeling.

• uptake of glutamate requires oxygen • in hypoxic conditions (eg stroke), glutamate remains in the cleft • toxic effect as it builds up

• presynaptic receptors bind NT released by cell, reduce amount of NT released with each AP, tones things down - site for drugs • post synaptic receptors send RETROGRADE signals to decrease NT release

cells that fire together, wire together x

When useful synapses are strengthened - increased plasticity

• more receptors • receptor function improved • more transmitter made • more transmitter released

Secondary messengers from activation of metabotropic receptors enhance long-term potentiation process.

Some excitable cells fire spontaneous bursts of action potentials, due to unstable membrane potential - in the heart for example.