Brain and behavior, environment of the neuron Homeostasis • is the process of ensuring that bodily variables stay within a preferred range • endocrine, nervous, immune systems Homeostasis – nervous system • brain is „smart“ – when possible anticipate challenges to homeostasis → all anticipatory homeostatic adjustments require intact forebrain • unexpected challenges to homeostasis → are met by largely unconscious reflexes mediated by the spinal cord and/or brainstem Homeostasis – nervous system • unconscious – e.g. peristalsis .... • voluntary – e.g. stable core body temperature Homeostasis – nervous system • functions based on interactions with external environment require behavioral component and are results of neuronal processing • behavior (from simple to complex) requires contribution of three main components: sensory, executive, motivational Goal directed behaviour • energetic balance • volume and osmolarity • temperature • performance • strenghthen health • reproduction • defense • ........... „Function“ is only approximation. • Nervous system works as a whole, no parts of the NS operates in isolation. • A single neural area or pathway may serve integrally in one or a few core functions but also contributes to countless other functions. → injury to one region can impact perhaps minutely or perhaps hugely many functions. Neuron • approx. 1011 of nerve cells (glial cells are 10 times frequent) • the most consistent neuronal trait is individuality • neurons differ from one another in location, morphology, connections, physiological characteristics • cells within localized clusters (nuclei) or layers (laminae) often share many common characteristics Most neurons share a group of traits: • four morphological regions – dendrites, body, axon, synaptic terminals • four functional components – input, integrative, conductile, output • generate regenerative electrical potentials • communication with another neurons Neuron – interesting numbers • an average somatic diameter of 5-25 microns • axonal diameter varies from 0.5-20 microns • the longest axons about 1.4 meters If we represent the soma (25 microns) by a baseball (ca. 12 cm) what proportionally would be the length of the 1 m axon ? Cell membrane • fosfolipid doublelayer • ion channels • transporters • receptors • synaptic membrane proteins Glial cells • CNS - oligodendrocytes, astrocytes, microglial cells • PNS - Schwann cells • Critical for development of NS functions: metabolic, immune, homeostatic Myelin Myelin insulate axons – rapid conduction of AP. Problems: the myelin wrapping can loosen, the immune system may attack and break down myelin → demyelination – impairment of neuronal communication (multiple sclerosis in CNS, Guillain Barré syndrom – peripheral demyelinating disease) Internal environment of CNS • extracellular space: intersticial fluid (15 % of brain volume) • ventricles and subarachnoidal space: cerebrospinal fluid (CSF) – clear and colorless, up to 4 cells/μl, relatively little proteins • function: homeostatic, protective, mechanical, (information transfer – neuropeptides ?) – 450-550 ml/day (70 % is produced in plexus choriodei) – circulating volume: 130-150 ml Brain barriers - notes • blood-brain and blood-CSF barriers • barriers keep constant composition of ECF and CSF • clinical implication: drug penetration – ATB, dopamin x L-Dopa • diseases can change barriers function • circumventricular organs – secretory function • posterior pituitary (eg. vazopresin) • pineal gland (melatonin) – physiology parameters monitoring • area postrema - chemoreception, vomiting • subfornical organ - osmolarity of blood, thirst Following the nutrients • the brain (approx. 3% of body`s mass) requires a steady and considerable supply of oxygen and glucose • consumption: 25% of body`s oxygen • without oxygen: unconsciousness after 10 seconds; irreparable damage after only a few, less than 5 minutes (note: vegetative structures in the brainstem are more resistant to hypoxia) • arterial blood flow to the brain represents about 15-20% of cardiac output = cerebral blood flow Energy sources • glucose (does not need insulin) • under starvation and diabetes also ketone bodies • new-borns also FFA during breastfeeding Synaptic transmission • synapses - communication between neurons and between neurons and target cells • chemical x electrical synapses • neurotransmitters Synapse • termed by Sir Charles Sherington (1932 – Nobel Prize in Physiology or Medicine) • average neuron forms about 1000 (2000) synaptic connections and receives as many as 10.000 connections • dendritic spines Chemical synapse • presynaptic cell • synaptic cleft: 20-40 nm • postsynaptic cell • synaptic delay: 1-5 ms (can be as short as 0.3 ms) • unidirectional Chemical transmission – 4 steps • presynaptic neuron: – the synthesis of a transmitter substance – the storage and release of the transmitter • postsynaptic neuron: – transmitter`s interaction with a receptor – removal of the transmitter from the synaptic cleft Transmitter • it is synthetized in the neuron • it is present in the presynaptic terminal and released to exert a defined action • a specific mechanism exists for removing it from its site of action (eg. difussion, enzymatic breakdown) Receptors • postsynaptic and presynaptic receptors (autoreceptors) • ionotropic and metabotropic receptors • each neurotransmitter: more types of receptors Ionotropic receptors – nAChR, GABAA,C , glycin, 5-HT3, glutamate – usually fast – open ion channels – motor actions and sensory processing Metabotropic receptors – slow, seconds - minutes – open and close channels – modulation of synaptic transmission – emotional states, mood, arousal, simple forms of learning and memory Neurotransmitters • Neurotransmitters: – excitatory - glutamate – inhibitory - GABA in brain, glycin in spinal cord • Neuromodulatores – serotonin, dopamin, noradrenalin, acetylcholin, histamin Peptide neurotransmitters • brain/gut peptides – substance P • opioide peptides – Leu-enkephalin • pituitary peptides - ACTH • hypothalamic releasing hormones - ACR • other peptides