Excitation and Inhibition Compete to Control Spiking during Hippocampal Ripples: Intracellular Study in Behaving Mice

Abstract

High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation of the rhythm and the recruitment of spikes from pyramidal neurons are still poorly understood. Using intracellular, sharp electrode recordings in freely moving, drug-free mice, we observed consistent large depolarizations in CA1 pyramidal cells during sharp wave ripples, which are associated with ripple frequency fluctuation of the membrane potential ("intracellular ripple"). Despite consistent depolarization, often exceeding pre-ripple spike threshold values, current pulse-induced spikes were strongly suppressed, indicating that spiking was under the control of concurrent shunting inhibition. Ripple events were followed by a prominent afterhyperpolarization and spike suppression. Action potentials during and outside ripples were orthodromic, arguing against ectopic spike generation, which has been postulated by computational models of ripple generation. These findings indicate that dendritic excitation of pyramidal neurons during ripples is countered by shunting of the membrane and postripple silence is mediated by hyperpolarizing inhibition.

Degeneracy in hippocampal physiology and plasticity

“…In addition, despite perpetual changes in afferent activity under in vivo conditions (Buzsaki, 1986(Buzsaki, , 1989(Buzsaki, , 2002(Buzsaki, , 2006Buzsaki et al, 1992;Csicsvari et al, 1999;English et al, 2014;Grosmark et al, 2012;Louie and Wilson, 2001;Mizuseki et al, 2011;Montgomery et al, 2008;Srikanth and Narayanan, 2015;Tononi and Cirelli, 2006;Wilson and McNaughton, 1994;Ylinen et al, 1995a), specific neuronal subtypes maintain distinct functional signatures, say in terms of their excitability or oscillatory or frequency selectivity measurements, that are different from other neuronal subtypes even in the same brain region Shepherd, 2002, 2005;Johnston, 2007, 2008;Pike et al, 2000;Spruston, 2008;Zemankovics et al, 2010). Further, synaptic peer-reviewed) is the author/funder.…”

“…For instance, they manifest strong oscillations in the theta frequency range (4-10 Hz) during exploratory behavior and during rapid eye moment (REM) sleep, and show characteristic sharp-wave ripple patterns during rest and non-REM sleep. These distinct activity patterns have been postulated to serve specific functions such as in the consolidation of memory and in neural encoding of space (Buzsaki, 1986(Buzsaki, , 1989(Buzsaki, , 2002(Buzsaki, , 2006(Buzsaki, , 2015Buzsaki and Moser, 2013;Colgin, 2013;English et al, 2014;Grosmark et al, 2012;Hartley et al, 2014;Lisman and Jensen, 2013;Mizuseki and Buzsaki, 2014;Montgomery et al, 2008;Moser et al, 2008;Moser et al, 2015;Tononi and Cirelli, 2006;Wilson and McNaughton, 1994;Ylinen et al, 1995a;Ylinen et al, 1995b).…”

Whole-Cell Recording in the Awake Brain

“…The recordings could survive severe mechanical disturbances and remain stable for 20 min while rats explored their environment freely. Other groups have shown that sharp intracellular recordings could be obtained and maintained in freely moving birds (Long et al 2010;Hamaguchi et al 2014;Kosche et al 2015;Vallentin and Long 2015) and mice (English et al 2014;Schneider et al 2014) using a head-mountable linear microdrive. The first such recordings were made from bird premotor HVC neurons to measure the subthreshold membrane potential dynamics during singing, and the resulting recordings supported a synaptic chain-like mechanism for birdsong generation (Long et al 2010).…”

“…High-quality and long-duration recordings of both types have been obtained successfully. There is, at present, no indication of differences in overall success rates when considering the latest versions of the methods applied to the same brain region (e.g., hippocampal subregion CA1) of the same species (e.g., mice) (English et al 2014;Lee et al 2014), although differences might emerge with increased use. However, there are some technical differences inherent to each approach.…”

“…Thus, it had not been straightforward to link the accumulated knowledge regarding synaptic and intrinsic mechanisms from experiments conducted mostly in vitro with higher brain functions that generally involve active participation of the animal. The development of intracellular recording methods for awake behaving animals across multiple species (Covey et al 1996;Fee 2000;Aksay et al 2001;Margrie et al 2002;Wilson et al 2004; Lee et al 2006Lee et al , 2014Harvey et al 2009;Long et al 2010;English et al 2014;Tan et al 2014) has therefore played and will continue to play a critical role in understanding the neural basis of cognitive processes (for a review, see Long and Lee (2012)). …”