title: 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 dorsal 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 that 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.SIGNIFICANCE STATEMENTDifferences in short- and long-term plasticity at Schaffer collateral (SC) synapses in the dorsal and ventral hippocampus likely contribute importantly to the distinct roles of these regions in cognition and behavior. Although dorsal and ventral CA1 pyramidal cells exhibit markedly different gene expression profiles, how these differences influence plasticity at SC synapses is unclear. Here we report that increased mRNA levels for the SK3 subunit of SK-type K+channels in ventral pyramidal cells is associated with an enhanced activation of SK channels that strongly suppresses NMDAR activation at ventral SC synapses. This leads to striking differences in multiple aspects of synaptic transmission at dorsal and ventral SC synapses and underlies the reduced ability of ventral SC synapses to undergo LTP.
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Walter E
authors.identifier: 0000-0001-5309-9196
authors.initials: WE
authors.lastname: Babiec
authors.affiliation: Molecular, Cellular, and Integrative Physiology Interdepartmental PhD Program, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Shekib A
authors.identifier: 0000-0001-5478-1963
authors.initials: SA
authors.lastname: Jami
authors.affiliation: Interdepartmental PhD Program for Neuroscience at University of California, Los Angeles, Los Angeles, California 90095, and.
authors.forename: Ryan
authors.initials: R
authors.lastname: Guglietta
authors.affiliation: Interdepartmental PhD Program for Neuroscience at University of California, Los Angeles, Los Angeles, California 90095, and.
authors.forename: Patrick B
authors.identifier: 0000-0002-2460-690X
authors.initials: PB
authors.lastname: Chen
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, todell@mednet.ucla.edu.|Integrative Center for Learning and Memory, Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Thomas J
authors.identifier: 0000-0002-9231-8694
authors.initials: TJ
authors.lastname: O'Dell
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018683:Excitatory Amino Acid Agents; C496898:Kcnn2 protein, mouse; C496900:Kcnn3 protein, mouse; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D051640:Small-Conductance Calcium-Activated Potassium Channels; C494303:Syt7 protein, mouse; D050857:Synaptotagmins
keywords: EPSP amplification; EPSP-spike coupling; NMDA receptor; SK channel; complex-spike bursting; hippocampal LTP