title: Enhanced auditory reversal learning by genetic activation of protein kinase C in small groups of rat hippocampal neurons.
abstract: The hippocampus has a central role in specific types of learning, but there is only limited evidence identifying the requisite molecular changes in ensembles of hippocampal neurons. To investigate the role of protein kinase C (PKC) pathways in hippocampal mediated learning, a constitutively active, catalytic domain of rat PKC betaII was delivered into hippocampal dentate granule neurons using a Herpes Simplex Virus (HSV-1) vector. This PKC causes a long-lasting, activation-dependent increase in neurotransmitter release from cultured cells. Activation of PKC pathways in a small percentage (< or =0.26%) of dentate granule neurons was sufficient to enhance rat auditory discrimination reversal learning. The affected neurons altered hippocampal physiology as revealed by elevated NMDA receptor densities in specific hippocampal areas. Thus, these results directly suggest that activation of PKC pathways in a specific hippocampal area alters rat auditory discrimination reversal learning. Because each rat may contain a unique pattern of affected neurons, there appears to be considerable flexibility and/or redundancy in the groups of neurons that can modify learning.
authors.affiliation: Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Neill
authors.forename: M R
authors.initials: MR
authors.lastname: Sarkisian
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: P
authors.initials: P
authors.lastname: Tandon
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: G L
authors.initials: GL
authors.lastname: Holmes
authors.forename: A I
authors.initials: AI
authors.lastname: Geller
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D003216:Conditioning, Operant / Q000502:physiology; D003720:Densitometry; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D004193:Discrimination Learning / Q000502:physiology*; D004789:Enzyme Activation; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000235:genetics; D017470:Receptors, Glutamate / Q000096:biosynthesis / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D018139:Simplexvirus / Q000235:genetics; D015854:Up-Regulation
chemical_list: D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D011493:Protein Kinase C; D064546:Protein Kinase C beta