Neuronal signalling- 3 lectures Dr Bill Phillips, Dept of Physiology Synapses and neuronal signalling Local signalling in neurons Excitability and Initiation of neuronal signals Kandel, Schwartz & Jessell, Principles of Neural Science 4th Edn Cpts 2,7,8,9

Synapses and neuronal signalling- General Dr Bill Phillips, Dept of Physiology Neuronal connections and their activity patterns give rise to behaviour Glial function The 4 functional domains within a neuron Signalling networks underlie specific behaviours Electrical nature of neuronal signalling Different types of information are conveyed using similar signals carried by distinct pathways Gene expression creates diversity and change in neuronal function

Neuronal connections and their activity patterns give rise to behaviour Sensation Interneuron network activity Motor system interneuron activity Motor response Central processing

Glial functions Structural support and insulation of neurons Myelin sheaths- Oligodendrocytes & Schwann Scavenging dead cells- microglia Housekeeping tasks- eg uptake of released neurotransmitters Radial glia direct migration of developing neurons Regulating the properties of presynaptic nerve terminals Blood brain barrier- astrocytes Trophic support for neurons?

The 4 functional domains within a neuron Input region/s for depolarising membrane currents (excitatory synapses or sensory receptor channels) Trigger zone integration of depolarising signals to initiate action potentials or not Propagation region- axon or sensory fibre Chemical release zone- transmitter or hormone release terminal

Signalling networks underlie specific behaviours Specific information processing tasks arise out of patterns of interconnections among neurons Both excitatory and inhibitory connections are involved in achieving functional outcomes Simple reflex responses are organised within spinal segments but sensory information is also fed to higher centres

Knee jerk reflex Sensory receptors in extensor muscle send signals centrally in response to stretch Excitatory (+ve) inputs to activate motor neurons to the extensor muscles Other sensory nerve terminals activate inhibitory interneurons that inhibit flexor motor neurons

Converging and Diverging inputs: common features of neuronal networks Each sensory fibre will form nerve terminals on multiple motor neurons from several extensor muscles (divergence) Multiple sensory nerves will contact each motor neuron allowing it to take account of a wider range of stretch information (convergence)

Inhibitory interneurons act in feed- forward and feed-back inhibition Feed-forward eg. Stretch afferent from extensor muscle acts through interneuron to inhibit activity of flexor motor neuron Feedback eg. Diverging axon branch of extensor motor neuron activates inhibitory interneuron that acts back to reduce firing of the motor neuron

Feed-forward inhibition Feed-back inhibition

Electrical nature of neuronal signalling Output of most neurons is a pattern of spikes (action potentials) Inside of neuronal membrane is normally electrically negative Action potential is a transient depolarisation of the cell membrane

Membrane is polarised at rest

Action Potentials: Basic mechanism Depolarisation at trigger zone initiates Hodgkin Cycle in local population of voltage-gated Na + channels (and/or Ca 2+ channels) Na + channel inactivation Delayed opening of voltage-gated K+ channels in response to depolarisation

Range of sensation is encoded in the frequency of ‘spikes’ If the trigger zone of a neuron is depolarised to ‘threshold’ one or more action potentials are initiated and propagate along the nerve fibre Action potentials typically occur in ‘trains of spikes (action potentials) The frequency of spikes is often determined by the degree of depolarisation.

Passive, triggering potentials vs the action potential

Different types of information are conveyed using similar signals carried by distinct pathways For sensory, motor and inter-neurons the nature of the signals (trains of spikes) is the same. Meaning of the signals is maintained by the distinct pathways of nerve fibres and their target nuclei in the brain.

Gene expression creates diversity and change in neuronal function Neurons differ most in the genes that they express Different combinations of ion channels, transmitter receptors Enzymes and genes for different transmitters Other proteins that influence excitability and synaptic function, adaptability Changes in expression of particular genes can modify the strength of particular synaptic inputs and outputs to alter behaviour of a neural network

Propagation of neuronal signals Dr Bill Phillips, Dept of Physiology Ion channels underlying action potential depolarisation and repolarisation Continuous and saltatory propagation Passive spread of depolarisation between Nodes of Ranvier Properties of the Nodes and Internodes Disorders affecting action potential propagation eg Multiple Sclerosis

Local signalling in neurons Active maintenance of the resting membrane potential Depolarising and hyperpolarising currents Input resistance of neurons determines the magnitude of passive changes in membrane potential Membrane capacitance prolongs the timecourse of signals Membrane and cytoplasmic resistance affect the efficiency of the spread of depolarising pulses Speed and efficiency of action potential propagation determined by passive membrane properties and axon diameter.

Active maintenance of the resting membrane potential Resting membrane potential of a neuron is maintained by a constant slow diffusion of K + out of the cell and Na + into the cell. Resting potential lies close to the Nernst Potential for K + the permeability of the resting membrane for K + is ~20fold greater than for Na +

Initiation of neuronal signals Dr Bill Phillips, Dept of Physiology Resting membrane potential Excitatory and inhibitory currents/potentials Passive properties of input parts of neurons Trigger zones and summation of synaptic potentials Role of inhibitory synapses Disturbances of neuronal excitability- eg epilepsy

Synapses I: Presynaptic mechanisms Dr Bill Phillips, Dept of Physiology Ca 2+ dependency of presynaptic neurotransmitter release processes Machinery of transmitter exocytosis Nature of the release event Vesicle recycling Presynaptic inhibition and autoinhibition Facilitation, potentiation of transmitter release

Synapses II: Postsynaptic Mechanisms Dr Bill Phillips, Dept of Physiology Types of ligand gated channels and their properties The dendritic spine as a receptor station for glutamate NMDA and non-NMDA glutamatergic responses Developmental and plastic changes at spine synapses Inhibitory GABA A and glycine receptor synapses

Neuromuscular disorders Dr Bill Phillips, Dept of Physiology Presynaptic acetylcholine release characteristics of the neuromuscular junction Postsynaptic membrane specialisations Synaptic acetylcholinesterase Myasthenia Gravis: causes and treatment Congenital Myasthenias- genes and synaptic function Prospects