1. VI. CNS Metabolic and circulatory features of the brain and CNS Electrophysiological properties of CNS neurons Neurotransmitters I: localization, synthesis, storage and transport Neurotransmitters II: release and neurotransmitter receptors Neurotransmitters III: transduction of neurotransmitter signals in the CNS The chemical senses: taste and smell Auditory physiology The vestibular system and somatosensory physiology Somatosensory physiology: pain and temperature Signal transduction and processing in the retina Signal processing and perception in the visual system Spinal reflexes Descending control of movement and posture Basal ganglia Cerebellum and cerebral cortex The reticular formation, reinforcement pathways, cortex, and EEG Sleep-wakefulness DOP: Higher cortical functions and imaging Learning and memory Lateralization of function, language and emotion Hypothalamic function I and II

2. CNS Physio

3. Brain Metabolism and Circulation 5.Cerebral blood flow increases in cases of a.influenza. b. hypoxia (Arterial P02= 75 mmHg). c.hypertension (Arterjal pressure= 140 mm Hg). d. coma. e. hypercapnia (Arterial PCO2 = 75 mmHg).

4. Regulation of Cerebral Blood Flow 60 120 60120180 Mean Arterial Blood Pressure (mmHg) Cerebral Blood Flow (ml/min/100g) Autoregulation of cerebral blood flow Hypercapnia Sympathetic nerve stimulation Remember Metabolic Hyperemia!

5. Electrophysiology of CNS Neurons The resting membrane potential for all brain neurons is: a.at an equilibrium state for potassium ions. b.at an equilibrium state for sodium ions. c.at an equilibrium state for chloride ions. d.a steady- state level between the equilibrium potentials of the ions involved, weighted by their relative permeabilities/conductances. e.is the same as the resting membrane potential for brain glial cells. Which of the following changes would increase the driving force for sodium entry into a neuron? a.depolarization of the membrane potential b.hyperpolarization of the membrane potential c.an increase in the extracellular sodium concentration d.The sodium equilibrium potential E Na becomes more positive. e.b, c and d are correct.

6. Membrane Potential Excitation is caused by: –Depolarization or Hyperpolarization –Increase in g K+ or g Na+ –Increase in ENa or EK

7. Major Neurotransmitters NameEffectSynthesisDegradationLocation GABAInhibitoryGAD from Glutamate Transported, GABA-T Ubiquitous GlutamateExcitatoryGluatminase, other TransportedUbiquitous AcetylcholineExcitatoryCholine, acCoA, CAT AchEBasal Foreb. Hippocampus Epi, NE, DAExcitatory (except  1 ) Tyrosine, THTrans, MAO, COMT NE- LC,Teg. DA- SN, Stri. Serotonin (5-HT) ExcitatoryTryptophan, TH Trans, MAOPons Raphe HistamineExcitatoryHistidine, (Decarboxyl) Transferase, MAO Hypothalamus PeptidesBothPrecursorsProteasesUbiquitous

8. Catecholamine Synthesis TyrL-DopaDANEEpi Tyr Hydroxylase AAADDbHPNMH MAO or COMT MHPG, VMA, HVA

9. Neurotransmitter Receptors GABA –GABA A Postsynaptic Cl - channel Agonists- Muscimol, Barbs, (Benzos) –GABA B G-protein-coupled, activates Adenylate Cyclase Axoaxonal inhibition. Prevents NT release GABA B - Pre Post GABA A GABA - NE (-)

10. Neurotransmitter Receptors Ach –Nicotinic Cation Channel (Ca ++ in CNS) Spinal Cord, Sup. Colliculus –Muscarinic G-protein-coupled, G i inactivates Adenylate Cyclase, G q activates PLC- Ca ++ influx M1- striatum, hippocampus, cerebrum M2- cerebellum

11. Somatosensory Mechanoreceptors (A  afferents) –Touch and Pressure (Slow Adapting) Merkel’s Disk Ruffini Corpuscles –Touch (Fast Adapting) Meissner’s (low-freq.) Hair Follicle Pacinian Corp. (high-freq.)- wide receptive field Proprioception Joint Receptors Dorsal Column-Medial Lemniscus

12. Pain Modulation Nociceptive Fibers (A  or C)synapse on SC neurons in the anterior horn (A). Descending 5-HT or NE neurons can modulate these synapses to prevent pain transmission.

13. Temperature Sense Cold (Ad) and Warm (C) fibers: –Enter the Spinal Cord at: Dorsolateral Lissauer fasciculus –Ascend and Descend –Cross SC through ventral w.c. to: contralateral ALS –Ascend through ALS to reticular formation, thalamus

14. Axonal Pain Reflex Paper P P P P Rubor- Red from enlarged arterioles (oxygenated blood) Dolor – Nociception Tumor – Swelling from extravasated fluid Type C (Also bradykinin)

15. Basal Ganglia Disturbances Parkinsonism –Degradation of DAergic neurons in SN –Tremor, akinesia, bradykinesia, cogwheel rigidity Huntington’s Chorea –Loss of intrastriatal med. Spiny GABAergics (caudate atrophy) –Chorea, dementia, deceased tone Ballism –Damage to STN (corpus luysii) - unilateral- hemiballismus –Flailing movements Athetosis –Damage to GP and Putamen –Wormlike, writhing movements, dystonia (posture issues) Tardive Dyskinesia –Iatrogenic side effect of neuroleptics (thorazine) –Involuntary mouth movements due to supersensitivity of DA receptors

16. Cerebellum Architecture (covered before) –Remember that climbing fibers from inferior olivary nuclei cause complex purkinje spikes, –Mossy fibers from other nuclei cause simple spikes in purkinje cells. Divisions –Cerebrocerebellum –Spinocerebellum –Vestibulocerebellum Deep nuclei (send out transmissions) –Fastigial, Interposed (globose,emboliform), Dentate, Lateral Vestibular Nucleus Granule Cells are the only excitatory ones! – Parallel fibers Cerebellar Lesions May Cause: 1.Motor Delay 2.Dysmetria (inaccuracy) 3.Dysdiadochokinesia (alternating movement disorders) 4.Intention Tremor, Ataxia, and Apraxia

17. Decorticate and Decerebrate Postures Decorticate: CNS Damage above level of Red Nucleus –Rubrospinal Tract active- activates arm flexors with response to pain or head turn in contralateral direction Decerebrate: CNS Damage at or below level of Red Nucleus –Everything extended except fingers.

18. The Human Retina Light changes 11-cis retinal to: –All-trans retinal This activates: –Transducin This activates –Phosphodiesterase This changes: –cGMP to GMP This causes: –Cation channels to close - hyperpolarization

19. Sleep Stages REM- –Sawtooth waves, mixed frequency EEG –Dreaming, Paralysis NREM- –Stage 1 – Low voltage, mixed freq –Stage 2 – Sleep spindles, K complexes –Stage 3 – Delta waves –Stage 4 – More Delta waves

20. Reticular Formation Raphe Nuclei –Serotonin SN, Ventral Tegmental Area –Dopamine –Nigrostriatal pathway – Motor Control –VTA-frontal cortex and VTA-nucleus accumbens Dopaminergic neurons overactive in schizophrenia Also important in reward effects of food, water, and drug abuse Locus Ceruleus: –Noradrenergic neurons control arousal and sleep- wake cycle

21. Learning and Memory AMPA vs. NMDA –AMPA Glu receptors are active during low- frequency stimulation –Na+ channels –NMDA channels require previous depolarization through AMPA channels, allow Ca++ in.