11There are Two Major Forms of Long Term Memory Explicit (Declarative)Implicit (Procedural)Requires Conscious AttentionMedial Temporal LobeHippocampusFacts and EventsPeople, Objects and PlacesDoes Not Require Conscious Attention But Often Requires Salience SignalsAmygdala, Cerebellum,Reflex PathwaysSkills andHabitsNonassociativeAnd AssociativeLearning
15Long Term Sensitization Leads to Altered Gene Expression and the The Gill Withdrawal Reflex has a Simple Stereotypical Internal Representation.Long Term Sensitization Leads to Altered Gene Expression and theGrowth of New Synaptic Connections.(5HT)(5HT)
16Long-Term Memory Requires a CREB1-Mediated Transcriptional Cascade
17Sensitization Produces Both Pre- and Postsynaptic Structural Changes in the Intact Animal (HRP) Sensitized
22There are Two Major Forms of Long Term Memory Explicit (Declarative)Implicit (Procedural)Requires Conscious AttentionMedial Temporal LobeHippocampusFacts and EventsPeople, Objects and PlacesDoes Not Require Conscious AttentionAmygdala, Cerebellum,Reflex PathwaysSkills andHabitsNonassociativeand AssociativeLearning
23Hippocampus of Humans Encodes Space Primrose HillRoute from Hyde Parkto Primrose HillHyde Park
25Multi Sensory Information About Spatial Memory is Only Brought Together in the CA1 Region of the Hippocampus
26The Hippocampal Pyramidal Cells Encode a Cognitive Map of Space :Is Attention Importand for Formation of the Map or for its Perpetuation
27Is Attention Important to Form the Spatial Map or to Stabilize and Perpetuate it? Four Degrees of Attention
28No Task (Basal Attention) Spatial Task (Maximum Attention) Selective Attention is not Required for the Formation of the Map but is Essential for its MaintenanceNo Task (Basal Attention)10 min3 HoursDay 1Spatial Task (Maximum Attention)
29Long Term Place Cell Stability Requires Selective Attention;Short Term Stability Does Not.
30EPSP Slope (% of control) LTP is a Candidate Synaptic Mechanism for Spatial Memory LTP has both an Early and a Late PhaseEPSP Slope (% of control)
32Both the Long-Term Memory for Spatial Context and the Long-Term Stability of the Place Cell Map Require PKALong Term Stability of the Place Cell Map1 h24 hSimilarity ScoreWTR(AB)Long Term Memory of Spatial Context% Freezing (5 min)1 h24 h
33Both Explicit and Implicit Memory Storage Use Modulatory Transmitters as a Salience Signal and a CREB-Mediated Transcriptional Switch for Converting Short-Term toLong- Term MemoryAplysia(bottom up modulation)Hippocampus(top down modulation)Where-PosteriorParietalCortexWhat-PrefrontalCortexHow is synapse specificity achieved? How is it maintained for the long term?
36Local Protein Synthesis is Required to Stabilize the In Addition to Transcription the Growth of New Synapses Requires 2 Local Marking SignalsTwo Marking Signals1. PKA for Growth2. Local Protein Synthesisfor StabilizationLocal Protein Synthesis is Required to Stabilize theLong Term Facilitation and the Growth of New Synapses
37The Cytoplasmic Polyadenylation Element Binding Protein Is a Regulator of Local Protein Synthesis that Can Activate Dormant Transcripts
38Properties of a “Prion” Protein (CPEB) 1) At least two distinct conformational states2) Conformational states are interconvertible3) One of the conformational states is dominant and can self-perpetuate epigeneticallyAB
39CPEB as a Candidate for the Self-Perpetuating Switch of Local Protein Synthesis CRE5 x 5HT1 x 5HTConformationBConformationAAAAAGrowthandproteins
40The “Prion-Like” Properties of Aplysia CPEB Are Different from Known Prions • The conversion from one state to the other is regulated by a physiological signal. • The dominant self-perpetuating state is the active state.•Aplysia CPEB might be representative of a new class of proteins with prion like properties, which has normal physiological function.
41Dopaminergic Stimulation Induces CPEB-3 Expression in the HippocampusCPEB-3Naive animalCPEB-3D1/D5 receptor agonist2 hr post injection
42Sensitization in Aplysia Spatial Memory in the Mouse Modulatory Transmitters Serve as Salience Signals to Stabilize Synaptic Plasticity and Behavior for Both Implicit and Explicit MemoryIs the mechanism for maintenance also general?Implicit Memory:Sensitization in AplysiaExplicit Memory:Spatial Memory in the Mouse