Lecture 3 - Neuronal Transmission, Brain & Behaviour PDF

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Neuronal TransmissionThe brain has roughly 100 billion neurons, with a complex circuitry that allows us to do all sorts of computations.Part 1: Resting potentialProperties of the neurons that are important for neuronal communication - Membrane potential: electrical charge across the membrane - At re...

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Lecture 3 Neuronal Transmission The brain has roughly 100 billion neurons, with a complex circuitry that allows us to do all sorts of computations. Structure of a Neuron - Dendrites: Recipient of information from other neurons - Soma: cell body, contains machinery that controls processing and integrates information - Axon: Carries information from the soma to the terminal button and hence to other cells. Axons can branch to contact multiple neurons - Terminal button: (buttons) found at the end of the axon, location of the synapse communication point with another neuron. Neuronal membrane - Boundary of soma, dendrites, axons, and terminal button. Separates the extracellular environment from the intracellular environment - Detects substances outside the cell

Part 1: Resting potential Properties of the neurons that are important for neuronal communication - Membrane potential: electrical charge across the membrane - At rest: difference between the inside and the outside of the neurons is approximately 60-70mV (millivolts) - At rest: inside is more negatively charged than the outside (inside of the membrane is -65 to -70mV) - Inside the neuron are organic anions that influence the neuron to be more negatively charged What causes there to be a membrane potential - The movement of particles across a membrane is due to the force of diffusion and the force of electrostatic pressure. Force of diffusion - Molecules move from an area of high concentration to an area of low concentration - Salt (NaCI); splits into two particles Na+ and CIForce of electrostatic pressure - Particles with a similar charge: repel - Particles with an opposite charge: attract Equilibrium Potential 1) P+ ions move across membrane by diffusion force 2) As P+ ions move there is an increase in electrical potential across the membrane (i.e. more +ve on one side, more -ve on the other).

Lecture 3 3) Eventually a point is reached when the diffusion force = electrostatic force. ‘Equilibrium potential’ is when outward movement = inward movement - Very few ions need to move to achieve this Resting membrane potential: -65-70mV 1) High concentration of Na+ outside the neuron, high concentration of K+ inside the neuron 2) At rest: more K+ channels open than Na+ channels because there are more K+ channels 3) Na+ moves into neuron and K+ out of neuron due to diffusion 4) As more K+ than Na+ can diffuse, the membrane come to rest near the K+ equilibrium potential (-85mV) The Nernst Equation - The equilibrium potential can be calculated for any ion using the Nernst equation - It’s the concentration of the ionic species outside versus inside that can influence the equilibrium potential. - If the ionic species is a greater concentration outside than inside, then the equilibrium is positive and if the outside is less than the inside then the equilibrium potential is negative The sodium potassium pump - Maintains the ionic concentration gradient (Na+ and K+) across the membrane and therefore resting potential How it works - Sodium takes an energy molecule called ATP which is broken down to release energy which forces the ions to move against their concentration gradient. - So takes sodium ions back outside of the cell and forces potassium ions back into the cell to maintain the concentration gradient of sodium and potassium cells so that they don’t all diffuse out or all diffuse in. Part II: Action Potential -

Nerve impulse Allows communication within the neuron, along the axon Generated at the axon hillock Generated either by the summation of converging inputs from the dendrites or by electrical stimulation (experimentally) Hyperpolarization and Depolarisation Hyperpolarization - when membrane potential becomes more negatively charged than at the resting membrane potential (RMP). Happens due to: a) Injection of small negative current b) When positive ions move out (K+) c) When negative ions move in (Cl -) Depolarisation - when membrane potential is more positive than RMP Happens due to: a) An injection of a small positive current

Lecture 3 b) Positive ions moving into the cell Action potential - Increase the size of the stimulation and therefore the degree of depolarisation - Once a threshold of depolarisation has been reached an action potential is fired, this is an all or none response. Voltage gated channels - Channels are voltage gated meaning that they are controlled by the voltage - Channels opened when the membrane becomes depolarised - Different degrees of depolarisation open the channels - Positive membrane potentials (very high degrees of depolarisation) results in an inactivation of the Na+ channels - We can look at these properties using voltage clamp experiments Voltage gated sodium channels - Closed at rest - There is an activation gate (m gate) and an inactivation gate (h gate) - If there is depolarisation the activation gate will open allowing sodium ions in - Once these reaches +30mV this reaches a refractory period where no more sodium ions can enter and the inactivation gate closes Voltage gated potassium channels - Closed at rest - It takes more depolarisation to open potassium channels than sodium channels - Potassium channels don’t have an inactivation gate like sodium channels put will eventually close after a certain point. Action potential summary 1. At the resting membrane potential, majority of the channels are closed 2. Small depolarisation opens a few Na+ channels. Na+ begins to move into the neuron (diffusion and electrostatic forces) leading to further depolarisation. 3. If the stimulation is large enough, majority of the Na+ channels open and more Na+ moves into the neuron (diffusion and electrostatic forces), again leading to further depolarisation. 4. As the neurone continues to depolarise, some K+ channels are opened allowing K+ to leave the neuron 5. At positive potentials the Na+ channels become deactivated (refractory) so that no Na+ can pass through. The remaining K+ channels open and K+ continues to leave the neuron driven by both diffusion and electrostatic forces (as inside the neuron is now positive.) 6. K+ continue to leave the neuron (diffusion). The membrane potential decreases and becomes negative. This is known as repolarisation 7. The K+ channels begin to close and the Na+ channels return to their closed normal state. The membrane potential drops to below the resting membrane potential due to a few remaining open K+ channels and the high concentration of K+ outside of the neuron. This is known as hyperpolarization. During this time another action potential is difficult to elicit. 8. The final K+ channels close and external K+ is diffused away. The membrane potential returns to the resting membrane potential. Na+ and K+ pumps working hard to restore resting membrane potential

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Part III: Myelination, synapses, receptors, and neurotransmitters Myelin sheath: fatty tube placed around the axon by either an oligodendrocyte or a Schwann cell Propagation of the action potential along the myelinated axon - Action potentials can only occur at the nodes of Ranvier as this is the only place where K+ and Na+ can pass through the channels - Depolarisation decays along the length of the myelinated sections - The depolarisation is built up at the Nodes of Ranvier and then it decays through the myelinated sections. However, when the impulse arrives as the next Node of Ranvier, there needs to be enough depolarisation to trigger another action potential. Advantages of myelinated axon - The generation of an action potential requires energy and time - Less action potentials are needed to send a nerve impulse along a myelinated neuron than an unmyelinated neuron Multiple sclerosis - due to damaged myelin sheath leading to loss of sensitivity, muscle weakness and difficulty with coordination and balance. Toxins Tetrodotoxin (puffer fish) blocks voltage gated sodium channels which means action potentials cannot pass through leading to paralysis and lungs not being able to move, and inability to breath leading to death and there is no cure. Dendrotoxin (Green mamba) blocks potassium gated channels meaning that action potentials run for longer leading to convulsions. The synapse Types 1. Electrical synapse: - Very rare in adult mammalian neurons - Junction between the neurons very small (3mm - gap junction) - Gap is spanned by proteins (connexins) which are used to communicate between the neurons (ions move freely) 2. Chemical synapses: - Common in adult mammalian neurons - Junction between the neurons 20-50nm - Chemicals (neurotransmitters) are released from the presynaptic neuron to communicate with the postsynaptic neurons Synapse locations - The presynaptic neuron is the one sending the message and the postsynaptic neuron receives the message Axodendritic synapse: - Activation of an excitatory synapse leads to local and small depolarization of the postsynaptic cell known as EPSP (excitatory postsynaptic potential). - EPSP decays over the length of the dendrite (decremental decay)

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Therefore, the closer the synapse is to the soma the greater its influence on the production of an action potential in the axon. - All inputs are summated at the soma (cell body). If there is enough excitation, then an action potential is generated at the axon hillock. Overview of processes at the chemical synapses 1. Action potential travels down the axon 2. When it gets to the synapse, depolarisation opens voltage-dependent calcium channels 3. Influx of calcium leads to neurotransmitter release 4. Neurotransmitter binds to and activates receptors on the dendrites of the postsynaptic cell 5. This leads to depolarization or hyperpolarization of the postsynaptic cells 6. This spreads to the postsynaptic soma, where summation occurs 7. If there is enough depolarisation, then an action potential is generated at the axon hillock. Neurotransmitters - Chemicals that are used to transmit information from the presynaptic neuron to the postsynaptic neuron Criteria 1. Chemical synthesized presynaptically 2. Electrical stimulation leads to the release of the chemical 3. Chemical produces physiological effect 4. Terminate activity Dales Law; If a particular neurotransmitter is released by one of a neuron’s synaptic endings, the same chemical is released at all synaptic endings of that neuron. Neurotransmitter release 1. Synaptic vesicle containing neurotransmitter ‘docked’ at the synaptic membrane 2. Depolarisation of the presynaptic neuron leads to the opening of calcium channels and calcium influx (concentration gradient) 3. Vesicles fuse with the synaptic membrane and releases neurotransmitter into the synapse 4. Vesicle detaches from the docking zone. Postsynaptic action of the Neurotransmitter - Neurotransmitter binds to receptors on the postsynaptic membrane, which affects the activity of the postsynaptic cell, the configuration of the receptors make them specific of different neurotransmitters. - Opening of an ionic channel (typically) Ionotropic receptor - Activates an internal 2nd messenger system that goes on to affect the functioning of the postsynaptic cell Metabotropic receptor. Ionotropic receptors Fast transmission - ion movement leads to an immediate change in the postsynaptic cell Excitatory fast transmission: - Movement of positive ions into the neuron (Na+) (e.g. Glutamate receptors) - Depolarisation - Excitatory postsynaptic potential (EPSP)

Lecture 3 Inhibitory fast transmission: - Ion channels opens - Movement of negative ions into the neuron (CI -) (e.g. GABA a receptors) - Hyperpolarization - Inhibitory postsynaptic potential (IPSP)

Metabotropic receptor Activation of a G - protein coupled receptor: 1. Neurotransmitter binds to receptor and activates the G-protein (exchange GDP for GTP) 2. G protein splits and activates other enzymes 3. The breakdown of GTP turns off G protein activity 4. Series of chemical reactions that leads to an amplification of the signal - second messenger system. Neurotransmitter deactivation Neurotransmitters must be inactivated after use to remove them from the synaptic cleft This is done through either 1. Reuptake 2. A Deactivating enzyme Major classes of neurotransmitters - Amino acids such as Glutamate, Aspartate, Glycine, GABA - Monoamines such as Dopamine Epinephrine, Norepinephrine which are all Catecholamines and Serotonin which is an indolamine - Soluble gasses e.g. Nitric oxide and carbon monoxide - Acetylcholine e.g. Acetylcholine - Neuropeptide Glutamate - Major fast excitatory neurotransmitter in the CNS - Very widespread through the CNS - Activates different types of receptors: mGluR, NMDA, AMPA GBAB - Major inhibitory neurotransmitter - Activates an ionotropic receptor which opens a chloride channel leading to hyperpolarisation Drugs enhance its function - Ethanol - Benzodiazepine - Barbiturate - Neurosteroids Neural integration: interaction of excitatory and inhibitory inputs - EPSP decays over the length of the dendrite, - Synapses close to the soma have a great influence as there is less opportunity for the signal to decay.

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EPSP can be decreased or abolished by IPSPs from inhibitory neurons that are active at the same time or can be enhanced by EPSPs from excitatory neurons that are active at the same time. Auto receptors - Located on the presynaptic terminal - Respond to neurotransmitter in the synaptic cleft - Generally, they are G-protein coupled - Don’t open ion channels - Don’t cause depolarisation - Regulate internal process controlling the synthesis and release of neurotransmitter - Negative feedback mechanism...