Neurophysiology - basic principles Tutorial II_autumn Most neurons share a group of traits: • derive from ectoderm • four morphological regions – dendrites, body, axon, synaptic terminals Most neurons share a group of traits: • derive from ectoderm • four morphological regions – dendrites, body, axon, synaptic terminals Most neurons share a group of traits: • four functional components – input, integrative, conductive, output • generate electrical potentials • communication with another neurons Axonal transport • apparatus for the protein synthesis in the cell body • orthograde/antegrade transport Glial cells Microglial cells • arise from macrophages • scavenger cells (remove debris resulting from injury, infection, …) Macroglial cells • Schwann cells (PNS), oligodendrocytes (CNS) - myelin CNS PNS Glial cells Microglial cells • arise from macrophages • scavenger cells (remove debris resulting from injury, infection, …) Macroglial cells • Schwann cells (PNS), oligodendrocytes (CNS) - myelin - blood vessels (tight junction formation → blood-brain barrier) - synapses and surface of nerve cells (produce tropic substances, maintain appropriate concentration of ions and neurotransmitters) • astrocytes – send processes to: Astrocytes • metabolic functions: K+, pH, oxidative stress (GSH), energy storage (glycogen), glutamate-glutamin shuttle • modulation of synaptic activity, tissue repair Cerebral Compartments Ganong´s Review of Medical Physiology, 23rd edition Blood-brain barrier cerebral capillaries – tight inter-endothelial connections circumventricular organs Cerebrospinal fluid - production rate of production: 450-550 ml/day (70 % come from plexus choriodei) circulating volume: 130-150 ml CSF pressure in supine position in lumbar region: 70-180 mmH2O Cerebrospinal fluid - composition clear and colorless, up to 4 cells/μl, little amount of proteins Cerebrospinal fluid: circulation Cerebrospinal fluid: absorption Resting membrane potential A difference in the electrical potential (=voltage) across the plasma membrane of an unstimulated excitable cell. Resting membrane potential the difference in electrical potential when the cell is at rest results from two factors: (1) the unequal distribution of electrically charged ions, in particular, the positively charged Na+ and K+ ions and the negatively charged amino acids and proteins, on either side of the cell membrane, (Na+-K+ pump) (2) the selective permeability of the membrane to K+ (ion channels). 3 Na+ 2 K+ nondiffusible anionts (proteins) + + + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - [Na+]e [Na+]i» [K+]e [K+]i« K+ Resting membrane potential Resting membrane potential ► Nernst equation Resting membrane potential 3 Na+ 2 K+ nondiffusible anionts (proteins) + + + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - [Na+]e [Na+]i» [K+]e [K+]i« K+ ► Goldmann equation Na+ Cl- [Cl-]e [Cl-]i Resting membrane potential Electrotonic potentials, local response … passive changes of membrane polarity caused by addition or removal of the charge by an electrode Electrotonic potentials, local response Action potential Guyton & Hall. Textbook of Medical Physiology Action potential … propagated electrical response of a nerve fiber (or other excitable cells), all-or-non character Action potential Action potential Action potential … propagated electrical response of a nerve fiber (or other excitable cells), all-or-non character Action potential Conduction orthodromic conduction saltatory conduction antidromic conduction Nerve fibres • … divided based on axonal diameter, conduction velocity, and function Synapses Many different axons converge on the neuron, and their terminal boutons form axodendritic and axosomatic synapses. Synapses - structure presynaptic membrane synaptic cleft postsynaptic membrane Synapses - types • electrical synapses • chemical synapses • excitatory synapses • inhibitory synapses • axo-dendritic, axo-somatic, axo-axonal synapses Synapses Excitatory postsynaptic potential (EPSP) Inhibitory postsynaptic potential (IPSP) Synapses Synapses - neurotransmitters Small molecule transmitters • large number of neuropeptides (substance P, enkephalin, vasopressin, etc.) Large molecule transmitters • monoamines (acetylcholine, serotonin, histamine) • catecholamines (dopamine, norepinephrine, epinephrine) • amino acids (glutamate, GABA, glycine) Synapses – neurotransmitters - receptors • Each neurotransmitter (ligand) has many subtypes of receptors – effects differ in cells. Synapses – neurotransmitters - receptors • Each neurotransmitter (ligand) has many subtypes of receptors – effects differ in cells. • Receptors are also on presynaptic membrane (autoreceptors) – feeback control (negative, less often positive). • Receptors tend to group in large families (structure and function) – ionotropic (ionic channel), metabotropic (Gproteins and proteinkinases) Synapses – neurotransmitters - receptors • Each neurotransmitter (ligand) has many subtypes of receptors – effects differ in cells. • Receptors are also on presynaptic membrane (autoreceptors) – feeback control (negative, less often positive). • Receptors tend to group in large families (structure and function) – ionotropic (ionic channel), metabotropic (Gproteins and proteinkinases) • Receptors are concentrated in clusters in postsynaptic membrane close to the place where the neurotransmitter is released. • Prolonged exposure to ligands results in desensitization of the receptors – homologous and hereologous. Synapses - neurotransmitters Monoamines • Intrinsic signals – e.g. rapid firing of the neuron • Extrinsic signals – e.g. direct synaptic input from other neurons, or diffuse action of neuromodulators Synapses – synaptic plasticity • Presynaptic modification – alteration of the neurotransmitter release • Postsynaptic modification – modulation of response to the neurotransmitter • Both pre- and postsynaptic modification at the same time • Short-term changes • Long-term changes – crucial to development and learning • Potentiation • posttetanic potentiation – increased size of EPSP during and after a repetitive (tetanic) stimulation of the presynaptic neuron (due to accumulation of Ca2+ and increased release of the transmitter) • may be long-term → long-term potentiation (learning) Synapses – synaptic plasticity • Potentiation Synapses – synaptic plasticity • Synaptic depression Synapses – synaptic plasticity • after a prolonged high-frequency stimulation - result from a temporary depletion of the store of releasable synaptic vesicles • Postsynaptic inhibition/facilitation Synapses – synaptic plasticity • release of excitatory/inhibitory neurotransmitter on the synapse → the probability of firing of the postsynaptic cell is increased/decreased • Presynaptic inhibition/facilitation Synapses – synaptic plasticity axo-axonal synapses Neuromuscular junction Neuromuscular junction Neuromuscular junction End-plate potential • local depolarizing potential due to increased Na+ conductance