We next examined the effect of the Syt1 KD on the electrophysiological activities of neurons in awake, freely moving mice. Hippocampal theta oscillations are critical for hippocampus-dependent learning and memory (Buzsáki, 2002 and Goutagny et al., 2009). Theta oscillations are generated by a combination of synchronized excitatory inputs to CA1 and local neuronal activity, especially the activity of local interneurons that may produce feedback inhibition onto medial septum neurons for pacemaking Apoptosis inhibitor of oscillations (Buzsáki,

2002). Recent studies indicated that theta pacemaking may originate in the CA1 region, providing further support for the hypothesis that CA1 region local neurons are critical for theta oscillation (Goutagny et al., 2009). The AAV infection in our experiments included all CA1 pyramidal cells and interneurons as well as most DG neurons (which influence CA1 region activity via direct innervation of CA3 region neurons), providing us with a system to evaluate the impact of manipulations of synaptic transmission on local oscillations. We recorded local field potentials in CA1 in awake, freely moving mice and found that TetTox significantly

reduced the power of theta oscillations, consistent with a critical role of the infected neurons in the generation of these oscillations (Figures 3A–3C). In contrast to TetTox, however, the Syt1 KD did not reduce the overall power of the oscillations but produced a shift in the peak frequency of click here the theta oscillations toward slightly higher frequencies (Figures 3A–3C). These results suggest that Endonuclease the residual synaptic release induced by spike bursts after the Syt1 KD is sufficient for the generation of theta oscillations. It appears likely that the change in synaptic transmission induced by the Syt1 KD altered the interaction between the hippocampus and septum (Buzsáki, 2002), thereby shifting the peak frequencies. Although it is premature to provide a mechanistic account for this observation, because the exact location

and mechanism of pacemaking of theta oscillations are not yet clear, these results further demonstrate that the Syt1 KD does not simply block the communication between neurons, but rather institutes a filter that permits selective propagation of high-frequency information. It needs to be noted that a small group of interneurons in the hippocampus express Syt2 instead of Syt1 (Kerr et al., 2008) and would not be affected by the Syt1 KD and may contribute to the generation of theta oscillations. To examine whether synaptic transmission mediated by isolated spikes and/or precise timing of synaptic transmission triggered by spike bursts in the hippocampus is essential for learning and memory, we tested the effect of the hippocampal Syt1 KD on contextual and cued fear conditioning.