Parallel processing of sensory cue and spatial information in the dentate gyrus.

During exploration, animals form an internal map of an environment by combining information about landmarks and the animal's movement, a process that depends on the hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal circuit where self-motion ("where") and sensory cue information ("what") are integrated, but it remains unknown how DG neurons encode this information during cognitive map formation. Using two-photon calcium imaging in mice running on a treadmill along with online cue manipulation, we identify robust sensory cue responses in DG granule cells. Cue cell responses are stable, stimulus-specific, and accompanied by inhibition of nearby neurons. This demonstrates the existence of "cue cells" in addition to better characterized "place cells" in the DG. We hypothesize that the DG supports parallel channels of spatial and non-spatial information that contribute distinctly to downstream computations and affect roles of the DG in spatial navigation and episodic memory.

Electrophysiological Correlates of Blast-Wave Induced Cerebellar Injury.

Understanding the mechanisms underlying traumatic neural injury and the sequelae of events in the acute phase is important for deciding on the best window of therapeutic intervention. We hypothesized that evoked potentials (EP) recorded from the cerebellar cortex can detect mild levels of neural trauma and provide a qualitative assessment tool for progression of cerebellar injury in time. The cerebellar local field potentials evoked by a mechanical tap on the hand and collected with chronically implanted micro-ECoG arrays on the rat cerebellar cortex demonstrated substantial changes both in amplitude and timing as a result of blast-wave induced injury. The results revealed that the largest EP changes occurred within the first day of injury, and partial recoveries were observed from day-1 to day-3, followed by a period of gradual improvements (day-7 to day-14). The mossy fiber (MF) and climbing fiber (CF) mediated components of the EPs were affected differentially. The behavioral tests (ladder rung walking) and immunohistological analysis (calbindin and caspase-3) did not reveal any detectable changes at these blast pressures that are typically considered as mild (100-130 kPa). The results demonstrate the sensitivity of the electrophysiological method and its use as a tool to monitor the progression of cerebellar injuries in longitudinal animal studies.

Anxiety Cells in a Hippocampal-Hypothalamic Circuit.

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.

Electrophysiological monitoring of injury progression in the rat cerebellar cortex.

The changes of excitability in affected neural networks can be used as a marker to study the temporal course of traumatic brain injury (TBI). The cerebellum is an ideal platform to study brain injury mechanisms at the network level using the electrophysiological methods. Within its crystalline morphology, the cerebellar cortex contains highly organized topographical subunits that are defined by two main inputs, the climbing (CFs) and mossy fibers (MFs). Here we demonstrate the use of cerebellar evoked potentials (EPs) mediated through these afferent systems for monitoring the injury progression in a rat model of fluid percussion injury (FPI). A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML) of the posterior cerebellum via multi-electrode arrays (MEAs). Post-injury evoked response amplitudes (EPAs) were analyzed on a daily basis for 1 week and compared with pre-injury values. We found a trend of consistently decreasing EPAs in all nine animals, losing as much as 72 ± 4% of baseline amplitudes measured before the injury. Notably, our results highlighted two particular time windows; the first 24 h of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~50% and 24%) were observed in the EPAs. In addition, cross-correlations of spontaneous signals between electrode pairs declined (from 0.47 ± 0.1 to 0.35 ± 0.04, p < 0.001) along with the EPAs throughout the week of injury. In support of the electrophysiological findings, immunohistochemical analysis at day-7 post-injury showed detectable Purkinje cell loss at low FPI pressures and more with the largest pressures used. Our results suggest that sensory evoked potentials (SEPs) recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels.

Spatial patterns of high-frequency oscillations in the rat cerebellar cortex.

Rhythmic signals in the brain have always intrigued neuroscientists and the cerebellum is not an exception. Cerebellar high-frequency oscillations have been explored over many decades, but underlying mechanisms have remained unclear. In this study, we have recorded spontaneous and evoked potentials from the cerebellar surface with chronically implanted, multi-electrode arrays. Evoked and spontaneous signals during behavior showed highly synchronized oscillations at ~150 Hz. Furthermore, this rhythmic activity displayed directional preference on the cerebellar surface. This preliminary study demonstrates the presence of highly synchronized cerebellar oscillations in high-frequency band that emerge episodically in anesthetized animals by sensory stimulation as well as during face cleaning in awake animals.

Differential effects of ketamine/xylazine anesthesia on the cerebral and cerebellar cortical activities in the rat.

Cerebellum is a highly organized structure with a crystalline morphology that has always intrigued neuroscientists. Much of the cerebellar research has been conducted in anesthetized animals, particularly using ketamine/xylazine combination in rats. It is not clear how and to what extent the cerebellar cortical circuitry is affected by this anesthesia. In this study, we recorded spontaneous and evoked potentials from the cerebellar surface with chronically implanted, flexible-substrate, multielectrode arrays in rats and compared them to the signals simultaneously recorded from the motor cortex with similar electrodes. The power spectra and the intercontact coherence plots of the spontaneous activity in the awake-quiet animals extended up to 800 Hz in the cerebellum and only up to 200 Hz in the motor cortex. Ketamine/xylazine anesthesia suppressed most of the activity in the cerebellar cortex, which was in clear contrast to the motor cortex. In the awake cerebellum, large coherence values were observed between contact pairs as far apart as ∼2 mm. Otherwise, there was not a discernable relation between the coherence and the intercontact distance. These results suggest that the surface electrodes can provide much more detailed information about the state of neural circuits when they are used on the cerebellar cortex compared with the cerebral areas. This may be due to the proximity of the molecular layer cells to the pial surface in the cerebellum.

Effect of anesthesia on spontaneous activity and evoked potentials of the cerebellar cortex.

Cerebellum is a highly organized structure with a crystalline morphology that has always intrigued neuroscientists. Much of the cerebellar research has been conducted in anesthetized animals, particularly using ketamine and xylazine combination. It is not clear how the cerebellar cortical circuitry is affected by anesthesia. In this study, we have recorded spontaneous and evoked potentials from the cerebellar surface with chronically implanted, flexible-substrate, multi-electrode arrays. The frequency contents of the spontaneous activity suggest that ketamine/xylazine anesthesia suppresses most of the components except those below 30 Hz. This preliminary study also showed that multi channels of cerebellar cortical activity can be recorded using flexible multi-electrode arrays in behaving animals, which is very challenging task with single microelectrodes.