Differential regulation of NMDA receptor-mediated transmission by SK channels underlies dorsal-ventral differences in dynamics of schaffer collateral synaptic function

Abstract

Behavioral, physiological, and anatomical evidence indicates that the dorsal and ventral zones of the hippocampus have distinct roles in cognition. How the unique functions of these zones might depend on differences in synaptic and neuronal function arising from the strikingly different gene expression profiles exhibited by dorsal and ventral CA1 pyramidal cells is unclear. To begin to address this question, we investigated the mechanisms underlying differences in synaptic transmission and plasticity at dorsal and ventral Schaffer collateral (SC) synapses in the mouse hippocampus. We find that, although basal synaptic transmission is similar, SC synapses in the dorsal and ventral hippocampus exhibit markedly different responses to θ frequency patterns of stimulation. In contrast to dorsa hippocampus, θ frequency stimulation fails to elicit postsynaptic complex-spike bursting and does not induce LTP at ventral SC synapses Moreover, EPSP-spike coupling, a process that strongly influences information transfer at synapses, is weaker in ventral pyramidal cells Our results indicate that all these differences in postsynaptic function are due to an enhanced activation of SK-type K+ channels tha suppresses NMDAR-dependent EPSP amplification at ventral SC synapses. Consistent with this, mRNA levels for the SK3 subunit of SK channels are significantly higher in ventral CA1 pyramidal cells. Together, our findings indicate that a dorsal-ventral difference in SK channel regulation of NMDAR activation has a profound effect on the transmission, processing, and storage of information at SC synapses and thus likely contributes to the distinct roles of the dorsal and ventral hippocampus in different behaviors.