Bidirectional synaptic plasticity in the dentate gyrus of the awake freely behaving mouse

Abstract

There is significant interest in in vivo synaptic plasticity in mice due to the many relevant genetic mutants now available. Nevertheless, use of in vivo models remains limited. To date long-term potentiation (LTP) has been studied infrequently, and long-term depression (LTD) has not been characterized in the mouse in vivo. Herein we describe protocols and improved methodologies we developed to record hippocampal synaptic plasticity reliably from the dentate gyrus of the awake freely behaving mouse. Seven days prior to recording, we implanted microelectrodes encapsulated within a lightweight, low profile head stage assembly. On the day of recording, we induced either LTP or LTD in the awake freely behaving animal, and monitored subsequent changes in population spike amplitude for at least 24h. Using this protocol we attained 80% success in inducing and maintaining either LTP or LTD. Recording from a chronic implant using this improved methodology is best suited to reveal naturally occurring brain activity and avoids both acute effects of local electrode insertion and drifts in neuronal excitability associated with anesthesia. Ultimately a reliable freely behaving mouse model of bi-directional synaptic plasticity is invaluable for full characterization of genetic models of disease states and manipulations of the mechanisms implicated in learning and memory.

Synaptic depression in the CA1 region of freely behaving mice is highly dependent on afferent stimulation parameters

“…The current finding that persistent synaptic depression cannot be elicited in CA1 sub-region of the freely behaving mouse is somewhat in contrast to the robust LTD that can be induced in vivo in the dentate gyrus of freely moving mice (Koranda et al, 2008). Even more striking in this case is the fact that whilst application of the classical afferent low-frequency electrical stimulation of 900 pulses at 1 Hz produces stark synaptic depression in the dentate gyrus (Koranda et al, 2008), the same protocol fails completely to induce any observable change in synaptic response in the CA1.…”

“…The current finding that persistent synaptic depression cannot be elicited in CA1 sub-region of the freely behaving mouse is somewhat in contrast to the robust LTD that can be induced in vivo in the dentate gyrus of freely moving mice (Koranda et al, 2008). Even more striking in this case is the fact that whilst application of the classical afferent low-frequency electrical stimulation of 900 pulses at 1 Hz produces stark synaptic depression in the dentate gyrus (Koranda et al, 2008), the same protocol fails completely to induce any observable change in synaptic response in the CA1. Although one of the obvious possibilities for the difference in the expression of LTD could be due to the region in question (i.e., CA1 vs. dentate gyrus), the more likely explanation is that in the intact hippocampus regulatory control restricts the range of afferent activities that lead to LTD, and in addition extrahippocampal neuromodulatory control may play an important part.…”

Frequency dependency of NMDA receptor‐dependent synaptic plasticity in the hippocampal CA1 region of freely behaving mice

“…Of the low number of in vivo studies already performed in freely behaving mice, most were conducted on the hippocampal dentate gyrus Errington et al, 1997;Jones et al, 2001;Koranda et al, 2008;McGehee, 2009;Tang and Dani, 2009;Zhang et al, 2010), whereas fewer studies have been performed on other hippocampal subregions that are also critical in information processing. The limited in vivo mice studies conducted on the CA1 have shown an association between long-term potentiation (LTP) and associative learning (Gruart et al, 2006;Gruart and Delgado-Garcia, 2007;Madronal et al, 2007Madronal et al, , 2012, but have yet to comprehensively address the oft-overlooked opposite end of the synaptic bidirectionality spectrum (Bear, 1996;Martin et al, 2000;Malenka and Bear, 2004), comprising long-term depression (LTD), which is known to be essential for other forms of learning (Kulla et al, 1999;Manahan-Vaughan, 2004, 2008b, in press;Goh and Manahan-Vaughan, 2012;Hagena and Manahan-Vaughan, 2012).…”

Long-term Potentiation of Perforant Pathway-dentate Gyrus Synapse in Freely Behaving Mice

“…While many studies of LTP in awake rats have been performed 3,4 , very few have been conducted in awake mice primarily due to the technical complexity posed by the limited cranial real estate in mice and the weight of electrode headstages relative to the average weight of mice 5 . The few studies that have demonstrated LTP in DG in freely behaving mice utilized either microdrive electrode systems or junction field effect transistor (jFET) preamplifiers integrated in the headstage which necessarily adds to the electrode payload burden to the animal [6][7][8][9][10] .…”