Hippocampal theta rhythm is believed to play a critical role in learning and memory. In animal models of temporal lobe epilepsy (TLE), there is evidence that alterations of hippocampal theta oscillations are involved in the cognitive impairments observed in this model. However, hippocampal theta frequency and amplitude at both the local field potential (LFP) and single unit level are strongly modulated by running speed, suggesting that the integration of locomotor information into memory processes may also be critical for hippocampal processing. Here, we investigate whether hippocampal speed-theta integration influences spatial memory and whether it could account for the memory deficits observed in TLE rats. LFPs were recorded in both Control (CTR) and TLE rats as they were trained in a spatial alternation task. TLE rats required more training sessions to perform the task at CTR levels. Both theta frequency and power were significantly lower in the TLE group. In addition, speed/theta frequency correlation coefficients and regression slopes varied from session to session and were worse in TLE. Importantly, there was a strong relationship between speed/theta frequency parameters and performance. Our analyses reveal that speed/theta frequency correlation with performance cannot merely be explained by the direct influence of speed on behavior. Therefore, variations in the coordination of theta frequency with speed may participate in learning and memory processes. Impairments of this function could explain at least partially memory deficits in epilepsy.

The ontogeny of neural substrates underlying episodic memory is not well described. Place cells are a surrogate for episodic memory and are important for spatial navigation in rodents. Although place cells are well described in mature brains, the nature of the maturation processes remains uncertain. We now report on the ontogeny of the place cell system in rats between P22 and P43, a time during which there is rapid improvement in spatial behavior. We found that place cells with adult like firing fields were observed at the earliest ages. However, at this age, adult like place cells were few in number and their place fields were not stable across multiple exposures to the same environment. Finally, independently of confounding factors such as the number of exposures to the environment, the proportion of adult-like place cells, their firing rate and their stability increased with age and the average spatial signal of all pyramidal cells improved. This finding could account for the poor spatial behavior observed at young ages (P20-P30) and suggests that a small number of adult-like place cells are insufficient to support navigation.The notion that hippocampus plays a critical role in the formation and storage of spatial memory is supported by the existence in rats (O'Keefe and Dostrovsky, 1971) and humans (Ekstrom et al., 2003) of neurons called place cells that encode the spatial location of the individual in the environment (Nadel, 1991;Rolls and Xiang, 2006). The place cell system has been suggested as a surrogate for episodic memory in humans (Eichenbaum et al., 1999) and place cell discharge properties provide useful access to the integrity of the networks supporting episodic memory. For instance, the signal quality of place cells (spatial coherence; (Kubie et al., 1990)) and the information content of their firing (Skaggs et al., 1993) provide information on the computational properties of these networks. In addition, place field stability across multiple exposures to the environment reflects the ability of these networks to consolidate information in memory. Currently it remains uncertain whether maturational processes are required for the establishment of a mature place cell network and if the timeframe of this maturation correlates with the already known development of spatial cognition. Establishing normal ontogeny of place cells is important as it may shed light on the phenomenon of infantile amnesia (Ruffman et al., 2001). In addition, neurological disease may impact developmental processes with long term adverse consequences and in Correspondence to: Rod C Scott, Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, One Medical Center Drive, Lebanon, New Hampshire 03756, Telephone: 603-650-4211, rscott@ich.ucl.ac.uk. Author ContributionsAll authors designed and carried out the experiments. R.C.S and P-P.L.S carried out the data collection and carried out the analyses. All authors wrote and approved the manuscript. NIH Public Access Author ManuscriptHippocampus. A...

Status epilepticus (SE) is a common neurological emergency, which has been associated with subsequent cognitive impairments. Neuronal death in hippocampal CA1 is thought to be an important mechanism of these impairments. However, it is also possible that functional interactions between surviving neurons are important. In this study we recorded in vivo single-unit activity in the CA1 hippocampal region of rats while they performed a spatial memory task. From these data we constructed functional networks describing pyramidal cell interactions. To build the networks, we used maximum entropy algorithms previously applied only to in vitro data. We show that several months following SE pyramidal neurons display excessive neuronal synchrony and less neuronal reactivation during rest compared with those in healthy controls. Both effects predict rat performance in a spatial memory task. These results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition.

Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior.