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
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 invitro. Here, we used Trpm4 knock-out (Trpm4−/−) rats to scrutinize TRPM4’s role in the intact brain invivo. After having confirmed the previous invitro 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