Superficial Layer-Specific Histaminergic Modulation of Medial Entorhinal Cortex Required for Spatial Learning

摘要: Abstract The medial entorhinal cortex (MEC) plays a crucial role in spatial learning and memory. Whereas the MEC receives dense histaminergic innervation from tuberomamillary nucleus of hypothalamus, functions histamine this brain region remain unclear. Here, we show that acts via H1Rs to directly depolarize principal neurons superficial, but not deep, layers when recording at somata. Moreover, decreases spontaneous GABA, glutamate, release onto superficial by acting presynaptic H3Rs without effect on synaptic deep layers. Histamine-induced depolarization is mediated inhibition Kir channels requires activation protein kinase C, whereas GABA depends voltage-gated Ca(2+) extracellular Ca(2+). Furthermore, microinjection H1R or H3R, H2R, antagonist respectively into impairs rat as assessed water maze tasks does affect motor function exploratory activity an open field. Together, our study indicates essential selectively regulating neuronal excitability transmission MEC.