title: Bidirectional NMDA receptor plasticity controls CA3 output and heterosynaptic metaplasticity.
abstract: NMDA receptors (NMDARs) are classically known as coincidence detectors for the induction of long-term synaptic plasticity and have been implicated in hippocampal CA3 cell-dependent spatial memory functions that likely rely on dynamic cellular ensemble encoding of space. The unique functional properties of both NMDARs and mossy fiber projections to CA3 pyramidal cells place mossy fiber NMDARs in a prime position to influence CA3 ensemble dynamics. By mimicking presynaptic and postsynaptic activity patterns observed in vivo, we found a burst timing-dependent pattern of activity that triggered bidirectional long-term NMDAR plasticity at mossy fiber-CA3 synapses in rat hippocampal slices. This form of plasticity imparts bimodal control of mossy fiber-driven CA3 burst firing and spike temporal fidelity. Moreover, we found that mossy fiber NMDARs mediate heterosynaptic metaplasticity between mossy fiber and associational-commissural synapses. Thus, bidirectional NMDAR plasticity at mossy fiber-CA3 synapses could substantially contribute to the formation, storage and recall of CA3 cell assembly patterns.
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Hunt
authors.forename: Nagore
authors.initials: N
authors.lastname: Puente
authors.forename: Pedro
authors.initials: P
authors.lastname: Grandes
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology; D034281:Dynamins / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004705:Endocytosis; D005260:Female; D007211:Indoles / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D007211:Indoles; D009419:Nerve Tissue Proteins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104077:metabotropic glutamate receptor type 1; D019319:Okadaic Acid; D004533:Egtazic Acid; D015763:2-Amino-5-phosphonovalerate; D010744:Phosphoric Monoester Hydrolases; D034281:Dynamins; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C000543:cyclopiazonic acid