Disentangling the role of TRPM4 in hippocampus-dependent plasticity and learning: an electrophysiological, behavioral and FMRI approach
Autor: | Silvia Pinto, Frank Angenstein, Marta Bovet-Carmona, Aurélie Menigoz, Tim Tambuyzer, Rudi Vennekens, Detlef Balschun, Jean-Marie Aerts, Karla Krautwald, Thomas Voets |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Long-Term Potentiation Functional magnetic resonance imaging Hippocampus Morris water navigation task Hippocampal formation Gene Knockout Techniques 0302 clinical medicine LTP induction genetics [TRPM Cation Channels] IN-VIVO Brain Mapping MEDIAL PREFRONTAL CORTEX General Neuroscience Long-term potentiation physiology [TRPM Cation Channels] Anatomy & Morphology FUNCTIONAL MRI Magnetic Resonance Imaging Anatomy Life Sciences & Biomedicine PERFORANT PATHWAY Histology TRPM4 physiology [Prefrontal Cortex] Prefrontal Cortex TRPM Cation Channels Biology Synaptic plasticity RAT HIPPOCAMPUS 03 medical and health sciences Memory Animals Learning ddc:610 physiology [Learning] TRPM4 protein rat ENTORHINAL CORTEX Science & Technology Dentate gyrus Neurosciences Excitatory Postsynaptic Potentials Rats Barnes maze SYNAPTIC-TRANSMISSION 030104 developmental biology DENTATE GYRUS nervous system Neurosciences & Neurology Neuroscience Transient receptor potential channels 030217 neurology & neurosurgery FEEDFORWARD INHIBITION |
Zdroj: | Brain structure & function 223(8), 3557-3576 (2018). doi:10.1007/s00429-018-1706-1 |
ISSN: | 1863-2661 1863-2653 |
Popis: | Hippocampal long-term potentiation (LTP) has been extensively studied as a cellular model of learning and memory. Recently, we described a central function of the Transient Receptor Potential M4 (TRPM4) channel in hippocampal LTP in mice invitro. Here, we used Trpm4 knock-out (Trpm4−/−) rats to scrutinize TRPM4’s role in the intact brain invivo. After having confirmed the previous invitro findings in mice, we studied hippocampal synaptic plasticity by chronic recordings in freely moving rats, hippocampus-dependent learning by a behavioral battery and hippocampal–cortical connectivity by fMRI. The electrophysiological investigation supports an involvement of TRPM4 in LTP depending on the induction proto-col. Moreover, an exhaustive analysis of the LTP kinetics point to mechanistic changes in LTP by trpm4 deletion. General behavior as measured by open field test, light–dark box and elevated plus maze was inconspicuous in Trpm4−/− rats. How-ever, they showed a distinct deficit in spatial working and reference memory associated to the Barnes maze and T-maze test, respectively. In contrast, performance of the Trpm4−/− in the Morris water maze was unaltered. Finally, fMRI investigation of the effects of a strong LTP induction manifested BOLD responses in the ipsilateral and contralateral hippocampus and the prefrontal cortex of both groups. Yet, the initial BOLD response in the stimulated hippocampal area of Trpm4−/− was significantly enhanced compared to WT rats. Our findings at the cellular, behavioral and system level point to a relevant role for TRPM4 in specific types of hippocampal synaptic plasticity and learning but not in hippocampal–prefrontal interaction ispartof: Brain Structure & Function vol:223 issue:8 pages:3557-3576 ispartof: location:Germany status: published |
Databáze: | OpenAIRE |
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