ABSTRACT
Cholecystokinin-expressing interneurons (CCKIs) are hypothesized to shape pyramidal cell-firing patterns and regulate network oscillations and related network state transitions. To directly probe their role in the CA1 region, we silenced their activity using optogenetic and chemogenetic tools in mice. Opto-tagged CCKIs revealed a heterogeneous population, and their optogenetic silencing triggered wide disinhibitory network changes affecting both pyramidal cells and other interneurons. CCKI silencing enhanced pyramidal cell burst firing and altered the temporal coding of place cells: theta phase precession was disrupted, whereas sequence reactivation was enhanced. Chemogenetic CCKI silencing did not alter the acquisition of spatial reference memories on the Morris water maze but enhanced the recall of contextual fear memories and enabled selective recall when similar environments were tested. This work suggests the key involvement of CCKIs in the control of place-cell temporal coding and the formation of contextual memories.
Subject(s)
Cholecystokinin , Hippocampus , Interneurons , Optogenetics , Pyramidal Cells , Animals , Male , Mice , CA1 Region, Hippocampal/physiology , CA1 Region, Hippocampal/cytology , CA1 Region, Hippocampal/metabolism , Cholecystokinin/metabolism , Cholecystokinin/genetics , Fear/physiology , Hippocampus/physiology , Interneurons/physiology , Interneurons/metabolism , Learning/physiology , Maze Learning/physiology , Memory/physiology , Mental Recall/physiology , Mice, Inbred C57BL , Mice, Transgenic , Pyramidal Cells/physiology , Pyramidal Cells/metabolism , Theta Rhythm/physiologyABSTRACT
With the advent of optogenetics, it became possible to change the activity of a targeted population of neurons in a temporally controlled manner. To combine the advantages of 60-channel in vivo tetrode recording and laser-based optogenetics, we have developed a closed-loop recording system that allows for the actual electrophysiological signal to be used as a trigger for the laser light mediating the optogenetic intervention. We have optimized the weight, size, and shape of the corresponding implant to make it compatible with the size, force, and movements of a behaving mouse, and we have shown that the system can efficiently block sharp wave ripple (SWR) events using those events themselves as a trigger. To demonstrate the full potential of the optogenetic recording system we present a pilot study addressing the contribution of SWR events to learning in a complex behavioral task.
Subject(s)
Behavior, Animal/physiology , Brain Waves/physiology , Electroencephalography/methods , Hippocampus/physiology , Learning/physiology , Optogenetics/methods , Animals , Female , Mice , Mice, Inbred C57BL , Pilot ProjectsABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0164675.].
