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NEUROBIOKIMIA: ASPEK BIOMOLEKULER DARI MEMORI

NEUROBIOKIMIA: ASPEK BIOMOLEKULER DARI MEMORI. Oleh Mohammad hanafi. Learning and memory. Learning : the process by which we acquire new knowledge. Memory : the process we retain that knowledge

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NEUROBIOKIMIA: ASPEK BIOMOLEKULER DARI MEMORI

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  1. NEUROBIOKIMIA:ASPEK BIOMOLEKULER DARI MEMORI Oleh Mohammad hanafi

  2. Learning and memory • Learning : the process by which we acquire new knowledge. • Memory : the process we retain that knowledge • In Aplysia, simple reflex could be modified by three different form of learning : habituation, sensitization, and conditioning. • ER Kandel first concentrate in sensitization. • Simple reflex  is simple learning  implicit learning  acquire implicit memory (non-declarative memory = procedural memory) • Theory on memory storage : 1.in the growth of new connection. 2.self-reexciting chain of neuron

  3. Implicit learning and memory • ER Kandel (from 1957 – still in progress) searching the molecular basic of memory storage. • In Aplysia, sensitization: a form of fear where by an aversive shock to the tail, recognized the stimulus as aversive and learns to enhance its defensive reflex responses to a variety of subsequent stimulus applied to the siphon, even innocuous stimulus. • A single shock gives rise to a memory last only minutes (short-term memory) • Four to five spaced shock to the tail  a memory lasting several days (long-term memory) • Short-term memory does not require synthesis of new protein, but long-term memory, it does require.

  4. Molecular mechanism Short-term sensitization • Stimulation of sensory neuron in the tail  activates specific interneuron that facilitate sensitization. Form contacts with axon of sensory neuron • Serotonin released by facilitating neuron bind to two types of G protein resceptors of ssensory axons. • Serotonin  GsR  ↑ cAMP  ↑ PKA  phosphorylate K+ channel  inactivate the hyperpolarizing K+ channel  (1) prolong action potential (2) ↑ duration of Ca2+ influx through voltage sensitive Ca2+-channel • Serotonin  GoR  activate phospholipase C (PLC)  formation DAG  activate PKC • PKA & PKC  phosphorylate L-type Ca2+ channel  open the channel

  5. The net effect ↑flow in Ca2+ into the axon  ↑ transmitter release  ↑ gill withdrawal Long-term sensitization • Repeated stimulation ↑ level cAMP  ↑PKA  recruits Mitogen-activated protein kinase (MAP) • PKA & MAP translocate to the nucleus • PKA phosphorylate & activate the transcription factor CREB1 (cAMP-response element-binding protein)  activates immediate-response genes for synthesis proteins ( 1. Ubiquitin hydrolase  PKA  persistent activity. 2. C/EBP (CAAT Enhancer Binding Protein = transcription factor  activate genes for synthesis protein  growth new synaptic connection

  6. Explicit learning and memory • Require conscious recall and concern with memory for people, place, and event. Involve the medial temporal lobe and structure deep to it hippocampus. • Hippocampus contain a cognitive map of space, lesion to it  interfere with spatial task. • Within hippocampus the Perforant pathway, Schaffer (Sch) collateral pathway, and Mossy fiber pathway • Stimulation of CA3 Sch collateral and recoded in CA1 – LTP (long-term potentiation) • LTP : 1.fundamental property of the majority of exitory synapses in the mammallian brain 2.synaptic change that may underlie learning and memory

  7. Early phase LTP is elicited with a single train of stimuli is given for one second at 100 Hz. Lasts 2 – 3 hours Late phase LTP after four trains stimuli separated by 10 minuts. Lasts >= 24 hours LTP : -occur in many parts of the brain due to increased synaptic efficiency -it function probably not only related to memory synapse specific -restricted to synapse that has been repeatedly used -comprised in two phases; a.short induction phase (short-term memory) b.late expression phase (long-term memory

  8. Molecular mechanism of LTP • Stimulation  (1)↑ dependent exocytosis of glutamate presynaptic neuron, post synapticly : (2) ↑ activation of AMPAR  (3) ↑ depolarization  relieves Mg blockage of NMDAR  ↑ Ca entry (4) activate mGlutR (=metabotropioc)  phosphorylation of NMDAR  further ↑ Ca entry (5) high entry Ca trigger Ca /calmodulin dependent Kinase, CK, PKC, and Fyn together  induces LTP (short-term explicit memory storage)

  9. Calcineurin : endogenous Ca2+- sensitive phosphatase  inhibitory costrain on expicit memory

  10. Single train Stimulation  act nNOS  retrograte Factor  ↑ Glu release

  11. Late phase LTP • Repeated stimulation ↑ level cAMP  ↑PKA  recruits Mitogen-activated protein kinase (MAPK) • PKA & MAPK translocate to the nucleus • PKA phosphorylate & activate the transcription factor CREB1 (cAMP-response element-binding protein)  activates effector for growth (tPA,BDNF) and regulator (C/EBPβ (CAAT Enhancer Binding Protein β)  synthesis protein  growth new synaptic connection

  12. Conclusion • Memory storage involves in the synaptic changes • Short-term memory storage (SMS) covalent modification of preexisting protein (no new protein synthesis)  ↑ synaptic strength • Long-term memory storage  protein synthesis  new synaptic connection • SMS implicit  serotonin; explicit  glutamate • LMS : implicit = explicit  PKA, MAPK, CREB-1

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