Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway

Abstract

Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS.

PET Mapping for Brain–Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes

“…Previous work indicated an essential role for the basolateral amygdala in stimulus-reward learning and for the dorsal hippocampus in spatial learning and memory (13). Interestingly, the current study found increased glucose metabolism not only in the amygdala and paraventricular thalamic nucleus but also in the septohippocampal nucleus and bilaterally in the lateral septumobservations that are consistent with recent literature on the hippocampus-to-lateral-septum pathway (14). The optogenetic stimulation of projections from the lateral septum to the lateral hypothalamus decreased locomotion, suggesting that the lateral septum has a crucial role in controlling locomotion and arousal.…”

Extended Amygdala to Ventral Tegmental Area Corticotropin-Releasing Factor Circuit Controls Binge Ethanol Intake

“…Importantly, when the Gi-DREADD was transduced in the BNST and CNO infused into the VTA, mice exhibited blunted binge-like ethanol drinking that was not evident in mice expressing the control virus in the BNST or following vehicle administration. And while we do not have definitive electrophysiological evidence of terminal CNO effects, as in vivo and ex vivo validation of such is inherently challenging, a number of recent studies have shown that terminal application of CNO does indeed alter behavior (25-27). Additionally, since this same treatment did not impact sucrose consumption, our results provide the first direct evidence that a CRF/GABAergic pathway form the BNST to the VTA selectively modulates binge-like ethanol drinking.…”

“…Mice were then injected with either a Cre-dependent control vector (AAV8-hSyn-DIO-mCherry, n=8) or the Cre-dependent G i/o -coupled DREADD vector (AAV8-hSyn-DIO-hM4d-mCherry, n=8) into the dorsolateral BNST. Mice were also implanted with bilateral cannulae aimed at the VTA to allow for selective activation of the DREADD infected terminals projecting from the BNST to the VTA (25-27). After allowing approximately 5 weeks for maximal viral vector transduction, DREADD protein expression, translocation and incorporation, the mice then underwent 2 more cycles of DID.…”

Multiple Running Speed Signals in Medial Entorhinal Cortex

“…Locomotion modulated firing rates have been observed in an overwhelmingly large number of cortical and subcortical structures (outside of motor generation regions), including primary visual cortex (Niell and Stryker, 2010), primary auditory cortex (Fu et al, 2014), barrel cortex (Fu et al, 2014) retrosplenial cortex (Cho and Sharp, 2001), posterior parietal cortex (Whitlock et al, 2012), postrhinal cortex (Furtak et al, 2012), entorhinal cortex (Sargolini et al, 2006; Wills et al, 2012; Kropff et al, 2015), striatum (Yeshenko et al, 2004), medial and lateral septum (King et al, 1998; Zhou et al, 1999), lateral hypothalamus (Bender et al., 2015) and the hippocampus (McNaughton et al, 1983). It is difficult to identify any single circuitry that could propagate running speed information throughout the hippocampal formation based on these varied structures, but recently glutamatergic neurons in MS were shown to be responsible for speed modulation in CA1 (Fuhrmann et al, 2015).…”