Chapter 4

• Neurons


  Consist of dendrites (antennae), cell body (factory), axon (wire) and terminal boutons (axon ending)

  
• How neurons communicate


  1. Action potential - brief electrical impulse

  2. Membrane potential - difference in electrical charge between the inside and the outside of the cell (about -70 mV)

  3. Neuron is said to be polarized

  
• Resting potential of a neuron

  • Four kinds of ions responsible: Na+, K+, Cl-, Protein-ions
  • Maintained by balance of diffusion and electrostatic pressure
  • Sodium-potassium transporter (pump) exchanges 3 Na+ out and 2 K+ in
  • Selective permeability of the neuronal membrane to K+ and Cl- but not Na+

  
• Action potential


  1. Membrane (axon hillock) must reach threshold of excitation (-55mV) to initiate

  2. Causes voltage-gated ion channels to open, first Na+ rushes in then K+ rushes out

  
• Conduction of nerve impulse

  • Action potential regenerated at each patch of the membrane down the axon
  • Local anaesthetics block sodium channels
• Synapse


  • Presynaptic cell, synaptic cleft, postsynaptic cell
  • Action potential causes calcium channels to open, releasing neurotransmitters into cleft
  • Neurotransmitters bind to postsynaptic receptors, triggering fast-acting or slow-acting changes
• Presynaptic effects


  • Autoreceptors (metabotropic)
  • Heteroreceptors (metabotropic) respond to chemicals released by postsynaptic or other neurons
  • Dispose of neurotransmitter from cleft by reabsorbing or breakdown by enzymes

  
• Fast-acting synaptic transmission


  • Ion channels (ionotropic)
  • Depolarization = excitatory postsynaptic potential (EPSP)
  • Hyperpolarization = inhibitory postsynaptic potential (IPSP)
  • Action potential depends on algebraic sum of all the inputs to the cell
• Slow synaptic transmission


  • Releases a chemical inside the cell (second messenger) (e.g. cAMP) (metabotropic)
  • May open ion channels or alter other aspects of cell functioning
  • G-protein sub-unit breaks off to trigger action
  • Longer acting than second messengers - kinases
  • Permanent changes - transcription factors (e.g. CREB, c-fos) alter expression of DNA
• Nervous system anatomy


  • Peripheral Nervous System (PNS) and Central Nervous System (CNS)
  • PNS has somatic (movement and sensory) and autonomic (sympathetic and parasympathetic) divisions

  
• Spinal cord


  • Long tube of neural tissue surrounded by vertebral column
  • Grey matter in middle - cell bodies; white matter - axons travelling up and down
• Hindbrain


  • Medulla Oblongata - controls breathing, heart rate, vomiting, salivation, coughing, sneezing
  • Locus Coeruleus - hind-brain nucleus, diffuse projections, NE, mood and arousal
  • Cerebellum - responsible for initiation and coordination of body movements, stores practiced motor programs
  • Reticular activating system - diffuse projection, important role in activation of the cortex
  • Raphe system - diffuse, serotoninergic, plays role in maintenance of sleep
  • Periaqueductal Gray - relays pain messages to cortex, rich in opiate receptors
• Midbrain


  • Ventral Tegmental Area (VTA) - dopamine neurons make up mesolimbic and mesocortical systems
  • Substantia Nigra - dopamine neurons make up nigrastriatal system projecting to basal ganglia

  
• Basal Ganglia


  • Striatum - caudate nucleus and putamen (input)
  • Globus pallidus - output to cortex
  • Involved in coordination of motor control
  • DA input from substantia nigra (nigrastriatal)
  • DA deficiency - Parkinson's Disease
• Forebrain


  • Limbic system - interconnected nuclei under the cortex, control of motivations and emotions
  • Hypothalamus - tiny, many nuclei controlling eating, drinking, sexual behaviour, temperature, fluid balance; controls pituitary gland
• Limbic system


  • Hippocampus - memory including spatial, may be important for place preference
  • Amygdala and septum - emotional significance
• Input from thalamus and cortex

  1. Globus palladus

  2. Output to cortex

  
• Motor loop


  Coordination of motor control
• DA deficiency


  Parkinson's Disease
• Limbic system


  • Interconnected nuclei under the cortex
  • Control of motivations and emotions (many drugs act here)
• Hypothalamus


  • Tiny, many nuclei (eating, drinking, sexual behaviour, temperature, fluid balance)
  • Fibre pathway (highway through hypothalamus) called medial forebrain bundle (MFB)
  • Animals love to stimulate MFB
  • Controls pituitary gland (master endocrine gland)
• Hippocampus


  Memory including spatial; may be important for place preference
• Amygdala and septum


  Emotional significance
• Amygdala


  Fear conditioning, site of action for anti anxiety drugs (e.g. benzodiazepines)
• Thalamus


  Sensory switchboard
• Cerebral Cortex


  • Immediately beneath the skull and surrounding the rest of the brain
  • Subserves a number of complex functions such as the integration of sensory information and the production of gross and fine movements
  • Lobes: frontal (decision making + motor), parietal (body senses), occipital (vision), temporal (auditory + complex vision)

  
• Brain Development


  • 1/4 of adult size by birth and almost to full size by age 1 year
  • Development is complex, involving cell production and differentiation (before birth), migration, and the formation of axonal connections – all under chemical control!
  • Drugs that cause malformations in the developing fetus are called teratogens
• Neurotransmitters


  • Monoamines
  • Catecholamines (Norepinephrine, Dopamine, Epinephrine)
  • Indoleamines (Serotonin)
  • Imidazoleamine (Histamine)
  • Acetylcholine
  • Adenosine
  • Endocannabinoids
  • Amino acids (GABA, Glycine, Glutamate, Aspartate)
  • Gaseous (NO, CO)
  • Peptides (Substance P, Opioid substances, Enkephalins, Endorphins, Somatostatin)

  
• Acetylcholine


  • Motor and other neurons are "cholinergic"
  • Basal forebrain complex (cortical activation and memory)
  • Pontomesencephalotegmental complex (REM sleep)
  • Many insecticides and nerve gases block the activity of acetylcholinesterase (AChE – enzyme to breakdown acetylcholine)
  • Nicotinic and muscarinic receptors
  • Curare – paralysis, Botox – muscle relaxation
• Biogenic Monoamines


  • Catecholamines (NE,DA) and the indolamine 5-HT
  • CA's produced from tyrosine, tyrosine hydroxylase rate-limiting
  • 5-HT is converted from tryptophan
  • Enzymes breaking down monoamines are called MAO and COMT
• Ways drugs effect monoamine transmission

  1. Blocks conversion of tyrosine to L-dopa (AMPT - antagonist)

  2. Blocks conversion of tryptophan to 5-HT (PCPA - antagonist)

  3. Blocks reabsorption of neurotransmitter (cocaine and some antidepressants - agonists)

  4. Blocks receptors (antagonists -- antipsychotic drugs block dopamine receptors; LSD blocks some types of 5-HT receptors)

  
• Mesolimbic (VTA to nucleus accumbens) and mesocortical (VTA to cortex) dopamine systems

  • Travel along MFB
  • Over activity of mesocortical contributes to schizophrenia (treat with dopamine antagonists)

  
• Nigrastriatal dopamine system


  • Projects from substantia nigra to the basal ganglia
  • Damage produces Parkinson's disease (treat with dopamine agonists like L-DOPA)
  • Overactive nigrastriatal system may be responsible for Tourette Syndrome
• Norepinephrine


  • Locus coeruleus
  • Arousal and attention
• Serotonin


  • Raphe nuclei
  • Mood, dreaming, aggression
• GABA


  • Universal inhibitory neurotransmitter
  • GABAA receptors opens chloride channel
  • 5 subunits, diverse because 15 subunits to choose from
  • Antianxiety drugs such as benzodiazepines enhance GABA receptors

  
• Glutamate


  • Major excitatory (receptors: kainate, AMPA, NMDA)
  • NMDA receptor has many binding sites other than glutamate
  • Mg2+ blocks unless membrane significantly depolarized, letting Ca+ through triggering long-term changes (e.g. memory mechanism)
  • PCP, ketamine act here

  
• Other small molecule neurotransmitters

  • Adenosine, 4 metabotropic receptors, wakefulness
  • Endocannabinoids (2-AG, anandamide), CB1 receptors are abundant, metabotropic, and involved in retrograde transmission, CB2 receptors in the periphery
  • Nitric oxide, soluble gas

  
• Peptides


  • Enkephalins (about 5 aa's) and endorphins (16-30 aa's) are two classes
  • Opiates (morphine and heroin) activate their receptors
  • Several types of metabotropic receptors
  • Analgesic and euphoric

  
• Electrical Recordings


  • EEG - Recording of electrical activity in the brain, which appears as waves of various widths and heights
  • ERP - EEG waves associated with a particular event or task averaged over a large number of trials
  • Advantage - Very good temporal resolution