How Real Neurons Work. Computational Neuroscience
The Neuron : Overview Thanks to Ramon y Cajal for the Neuron doctrine. (v. reticular theory). Principles of Dynamic Polarization : Signals flow only in one direction. Principle of Connectional Specificity : Neurons don’t make random connections. These doctrines are now being called into question. http://www.stewartartists.com/Pages/jjani_pc/jjnrns_pc.html
Inside a Neuron. • Most differentiated cells in the body. • Neurons develop from epithelial cells. • Proteins are synthesised in the cell body. • They are modified in the ER and Golgi complex and exported along the axon.
Classification of Neurons. Unipolar : Invertebrates. Bipolar : Retina, Olfactory epith., Multipolar : e.g. motor neuron, pyramidal cell, perkinje cell. • The Cytoskeleton determines shape of neuron, (disrupted in Alzheimer’s disease). • Dynamic microtubules and microfilaments.
The Resting Cell Membrane Ionic concentration gradient established by Na/K ATPase Pump (100 ions/s). K channels allow K to diffuse freely at a certain rate. K leaves the cell, so making the outside positive and the inside negative. This is self-limiting, as the positive external charge opposes the further efflux of K+ I.E 2 forces : Channel Driving Force, Electrical Driving Force, when balanced we have the Equilibrium Potentialof K+ . http://www.du.edu/~kinnamon/3640/memb_pot_1.html
Ion Channels Ion Channels are crucial for rapid membrane potential changes. Ion Channels are proteins that span the cell membrane. Q. How can a water-filled channel conduct at high rates and yet be selective to ions surrounded by their waters of hydration? A. • PROPERTIES. • Conduct Ions. • Recognize and select specific ions. • Open and close in response to specific electrical, mechanical or chemical signals. • Rapid rate of flow 108 /s • Opening and Closing of a channel involves conformational changes.
The Action Potential • http://www.blackwellscience.com/matthews/channel.html An Action Potential is due to channels opening and closing in a voltage dependent manner. Na channels open above a threshold voltage.
The Ceylon Puffer Fish Tetrodotoxin injected by Hodgkin and Huxley to block Voltage-gated Na Channels.
Cocaine From coca leaves was the first anaesthetic, and also blocks Na+ channels with lower affinity and specificity than tetradotoxin.
The K Channel • An outward K+ current increases the repolarization rate of the action potential Using Brownian dynamics simulations, we follow the trajectories of interacting ions in the potassium channel. With a fast supercomputer, we simulate the motion of 26 potassium ions and 26 chloride ions interacting through the intermolecular potential. Here we apply a potential difference across the channel such that inside is positive with respect to outside. The motion of each ion during each discrete time step is determined by, first, the net electrical force acting on it; secondly, the frictional force and, finally, random force originating from incessant collisions of the ion with its surrounding water molecules. • Variations in the properties of voltage-gated ion channels increase the signaling capabilities of neurons. • Gating of voltage gated ion channels can be influenced by cytoplasmic factors, e.g. with Ca2+ channels. An energy profile can be calculated based on molecular structure.
Propagation of Action Potential Is forwards, because of the inactivated Na channels. AP travels at 80m/s • PASSIVE ELECTRICAL PROPERTIES OF NEURONS : • Membrane Resistance determines the magnitude of passive changes in membrane potential. Related to [ion channel]. • Membrane Capacitance prolongs the time course of electrical signals. Related to surface area of cell. • Membrane and Axoplasmic resistance affect the efficiency of signal conduction.
Chemical Synaptic Transmission • When AP reaches a neurons terminal • It stimulates neurotransmitter release. • Output signal is graded, amount of NT released is determined by the number and frequency of the action potentials. • After release, NT diffuses across the cleft to receptors on the post-synaptic neuron. Binding then results in the post-synaptic cell generating a synaptic potential. The sign of this synaptic potential depends on the type of receptors.
Pre-Synaptic Mechanisms • Action Potential reaches Synapse. • Synaptic terminal is depolarized. • Voltage sensitive calcium channels open. • Calcium enters synaptic terminal. • Release of chemical neurotransmitter
Amanita muscaria A Muscurinic Agonist. Stimulates one of the receptors that AcetylCholine binds to. The Black widow spider (Latrodectus) is so toxic because of massive release of acetylcholine from neurones. Nicotine is a Nicotinic receptor agonist. Atropia Belladonna is used to achieve mydriasis, it has atropine which is an antagonist of muscarinic receptors Sweating, salivation, abdominal cramps, bradycardia
Post-Synaptic Mechanisms • Neurotransmitter binds to receptors. • Change in ionic permeability of post-synaptic cell. • Change in membrane potential of post-synaptic cell. • The same neurotransmitter can have different effects depending on the post-synaptic receptors present, i.e. inhibitory or excitatory.
Many Types of NT Receptor Exist. 1. Ionotropic 2. Metabotropic
Dendritic Spines. The video clip shows miniature synaptic calcium transients visualized with the fluorescent calcium probe (fluo-3) in a spiny cultured rat cortical neuron dendrite. The image shows activity over a 10 sec period.