Hippocampus And Amygdala Memory-related Receptor Gene

NMDA receptor plays a vital role in synaptic plasticity. Long-term potentiation (LTP), known as a synaptic mechanism of learning and memory, requires the activation of NMDA receptor in many regions, such as amygdala and hippocampus. In particular, it is suggested that NR2A subtype is involved in LTP induction, whereas NR2B in LTD induction in CA1 region. However, the roles of NR2A and NR2B subunits in memory are not well understood. Here, we investigated the effects of NR2A and NR2B subunits in amygdala and hippocampus on fear memory, respectively.1) We investigated the effects on fear memory of intra-BLA infusion of selective antagonist to NR2A or NR2B, or inhibiting the functions of NR2A or NR2B in BLA with gene delivery technology. Our results demonstrate that, both NR2A and NR2B in BLA are involved in acquisition of fear memory, but not in expression of the memory.2) We investigated the effects on fear memory of intra-CA1 of infusion of elective antagonist to NR2A or NR2B, a hippocampus-dependent task. Our data demonstrate that NR2A in area CA1 is required for both acquisition and expression of contextual fear memory, whereas NR2B is not important for acquisition, but is required for expression, of the memory.Tob (transducer of ErbB2) is a negative cell cycle regulator with anti-proliferative activity in the periphery. Using a behavioral screening paradigm to look for novel gene functions in the brain, we identified Tob as a brain-expressed protein involved in learning and memory. Behavioral training of fear-conditioning triggered a transient elevation of Tob protein, which preceded the formation of long-term memory. Functional perturbation of Tob by intra-CA1 infusion of antisense oligonucleotides in rats impaired spatial learning and memory in the Morris water maze and long-term memory for contextual fear conditioning, two behavioral paradigms that require the hippocampus. Furthermore, long-term potentiation was suppressed by Tob antisense infusion into the CA1 region. Together, these results indicate that the negative cell cycle regulator Tob is a multifunctional protein involved in hippocampus-dependent learning and memory.Memory formation, maintenance and retrieval are a dynamic process, reflecting a combined outcome of new memory formation on one hand, and older memory suppression/clearance on the other. Although much knowledge has been gained regarding new memory formation, less is known about the molecular components and processes that serve the function of memory suppression/clearance. Here we report the identification of a novel protein, termed hippyragranin (HGN), that is expressed in the rat hippocampus and its expression is reduced by hippocampal denervation. Inhibition of HGN by antisense oligonucleotide in area CA1 results in enhanced performance in Morris water maze, as well as elevated long-term potentiation (LTP). These results suggest that HGN is involved in negative memory regulator.Previous studies showed that β-adrenoceptors in amygdala are involved in the memory consolidation for emotional arousing experience and the activation of β-adrenoceptors in hippocampal CA1 region facilitates in vitro long-term potentiation (LTP). It is unclear if hippocampus-dependent learning is subjected to β-adrenergic regulation. Here, we studied roles of β-adrenoceptors in area CA1 in spatial learning and memory consolidation, and in synaptic plasticity in vivo.In Morris water maze experiment, pretraining blockade of β-adrenoceptors in area CA1, impaired spatial learning; 5-min, but not 6-h postraining blockade impaired 48-h spatial memory in rats, In electrophysiological experiment, the theta-pulse stimulation (10 Hz, 150 pulses/train, 1 train), a frequency that weakly modifies synaptic strength, induced a robust LTP when p-adrenoceptors in area CA1 were activated. By contrast, the theta-pulse stimulation (5 Hz, 150 pulses/train, 3 train), a frequency that vstrongly modifies synaptic strength, induced a significantly smaller LTP when β-adrenoceptors in area CA1 were blocked.Our results demonstrate that β-adrenoceptors in area CA1 are involved in regulating learning and memory in Morris water maze, and in vivo long-term potentioation.