Abstract
Hippocampal pyramidal neurons play an essential role in processing spatial information as implicated with its place-dependent firing. Although, previous slice physiology studies have reported that voltage gated calcium channels contribute to spike shapes and corresponding firing rate in the hippocampus, the roles of P/Q type calcium channels (Cav2.1) underlying neural activity in behaving mice have not been well-investigated. To determine physiological and behavioral roles of Cav2.1, we conducted place cell recordings in CA1 and hippocampus dependent learning/memory tasks using mice lacking Cav2.1 in hippocampal pyramidal neurons under CamK2α-Cre recombinase expression. Results suggested that impairments shown in behavioral tasks requiring spatial and contextual information processing were statistically significant while general neurological behaviors did not differ between groups. In particular, deficits were more profound in recognition than in acquisition. Furthermore, place cell recordings also revealed that the ability to recollect spatial representation on re-visit in the conditional knockout was also altered in terms of the cue recognition while the capability of a place cell to encode a place was intact compared to the control group. Interestingly, CA1 pyramidal neurons of conditional knockout mice showed reduced burst frequency as well as abnormal temporal patterns of burst spiking. These results provide potential evidence that Cav2.1 in hippocampal pyramidal cells modulates temporal integration of bursts, which, in turn, might influence the recognition of place field and consequently disrupt spatial recognition ability.
Highlights
Hippocampal pyramidal neurons exhibit location-dependent discharges, providing physiological evidence that the hippocampus is critical for spatial learning and memory (O’Keefe and Dostrovsky, 1971; O’Keefe, 1979)
All behavioral impairments of cKO were rather shown in hippocampal dependent tasks such as water maze and contextual fear conditioning tasks, but not in other tasks including Y-maze, open field and object recognition tasks, suggesting that behavioral roles of Cav2.1 in other forebrain regions, excluding the hippocampus, were considerably limited
While moderate impairment was shown during the acquisition of a water maze task, the performance in a contextual fear conditioning task was intact during the acquisition
Summary
Hippocampal pyramidal neurons exhibit location-dependent discharges, providing physiological evidence that the hippocampus is critical for spatial learning and memory (O’Keefe and Dostrovsky, 1971; O’Keefe, 1979). At the synaptic level, burst firing is functionally implicated in more successful information processing due to its stronger summation of excitatory post-synaptic potentials (EPSPs) and consequent reliable neurotransmitter release compared to a single spike (Xu et al, 2012). Burst spiking of hippocampal place cells is more spatially tuned when forming place fields compared to single spiking and relevant to hippocampal theta rhythm, as it takes up a high proportion of firing during 6–7 Hz oscillation (Harris et al, 2001). Despite several suggestions aforementioned about the functional roles of burst spiking on information processing and behavioral effects, its specific roles on spatial representation of hippocampal place cells and modulatory function on behavior have not been revealed yet
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