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Integration of neural plasticity

Integration of neural plasticity. Multiple mechanisms per synapse Multiple synapses per cell Multiple cells per function Examples Tritonia escape response Aplysia gill withdrawal reflex Leech central pattern generator Autonomic control of hypertrophy. Neural pattern generation.

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Integration of neural plasticity

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  1. Integration of neural plasticity • Multiple mechanisms per synapse • Multiple synapses per cell • Multiple cells per function • Examples • Tritonia escape response • Aplysia gill withdrawal reflex • Leech central pattern generator • Autonomic control of hypertrophy

  2. Neural pattern generation • Tonically firing neurons • Pacemaker cells • Persistent Na+ leak • Rhythmic neural circuits • Sensory feedback

  3. Central pattern generator • Rhythmic assembly of neurons • Coordinate cyclic movement patterns • Flexion-extension • Parystalsis • Self-organizing, independent of external feedback • Hierarchical • Entrainment • Sensory feedback • Higher neural process

  4. CPG Organization • Leech swimming by dorso-ventral flexion • Independent control of 32 segments CPG Motorneurons Friesen et al, 1976

  5. CPG signal propagation • Generalized “descending” excitation • Segmental coordination by inhibition Inhibitory connections run opposite direction of signal propagation Friesen et al, 1976

  6. Coordination • Intersegmental • Parallel PA inhibition as within segment • Conduction delay between segments

  7. Coordination • Sensory feedback • Nervous system needs state information • Subject to habituation, sensitization, etc • PSPs in LG or sol motorneuron due to synergist afferent. • IPSP in “resting” state • EPSP after dopamine This is a monosynaptic connection. Reversal with dopamine suggests that some dopaminergic interneuron changes the character of state feedback. EPSPs would extend the flexion half-center; IPSPs would shorten it. Gossard et al, 1994

  8. Autonomic control of arterial tone • Neuroanatomy • Neural signaling • Transmitters • Receptors • Secondary signaling

  9. Autonomic neuroanatomy • Principal effector system • Competitive • Sympathetic • Parasympathetic • Except skeletal muscle (somatic)

  10. Neuroanatomy Sympathetic Paravertebral Ganglion • Spinal cord • Preganglion • Sympathetic trunk • Postganglion • Ionotropic rcptrs • Perhipheral effectors • Metabotropic receptors Dorsal Root Spinal cord Ventral Root Sympathetic Trunk

  11. Autonomic signaling Co-Transmission and Co-localization with neuroactive peptides Tyrosine derivatives Tryptophan derivative

  12. Cerebrovascular Anatomy • Redundant • Carotid artery • Subclavian • Circle of Willis • Pressure regulation • Myogenic • Neurogenic Anterior Cerebral A Internal Carotid A Middle Cerebral A Basilar A Posterior Cerebral A Vertebral A Netter 1989

  13. Cerebrovascular innervation Sympathetic axons (white) surround various chick cerebral arteries. Hayashi et al. 2002

  14. Cerebral arteries • Myogenic and neurogenic regulation • Not all arteries are innervated • Peripheral vs Cerebral • Innervated via cerebral ganglion • Norepinepherine, serotonin, dopamine • Reduce flow during extreme stresses Tension 30 s Electrical stim Neurotransmitter bath

  15. NE Ca2+ Gq PLC Contraction Adrenergic vasoconstriction • G-Protein coupled activation of TRPC3 & PLC • IP3 mediated Ca2+ release • Parallel serotonin pathway • NE mediates bronchodilation, also via Gi Gi/o a1A-AR Gi 5-HT 5-HT1 Adayev et al, 2005 Lincoln 1995 Spitzbarth-Régrigny et al 2000

  16. Innervation mediates proliferation and differentiation of smooth muscle • Sympathetic denervation reduces cell # • Denervation reduces contractile proteins Untreated artery Sympathectomized

  17. 5-HT 1B/1D 5-HT 2A Growth-associated serotonin signaling 5-HT Extracellular Rho-GEF PI3K PLD PC PA Rho Kinase mTOR Cytoplasm ROCK RSK1 ERK S6 Hypertrophy Proliferation GATA4 Cyclin D1 ERK Elk1 Egr1 Liu &Fanburg (2004,6,8) Nucleus

  18. Physiological consequences • Vasoconstriction promotes hyperplasia • Wall thickening vs lumen dilation • Postnatal growth • Genetic polymorphisms • Adrenergic receptors • Exercise tolerance • Hypertension • G-Proteins • Hypertension • Body composition • GRK • Heart failure

  19. Pathology • Stroke • B-adrenergic receptor polymorphism may be a risk factor for ischemia • Other cerebrovascular incidents • Lower NE associated with intracerebral hemorrhage in brown Norway rats • High NE associated with aneurysm during experimental hypertension or hyperperfusion in Long Evans rats • Statins • Cholesterol reducing drugs also reduce farnesyl and geranyl-geranyl fatty acids • Rho acylation is essential for its function • Statins reduce VSM proliferation

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