During hippocampal inactivation, grid cells maintain synchrony, even when the grid pattern is lost.

The grid cell network in the medial entorhinal cortex (MEC) has been subject to thorough testing and analysis, and many theories for their formation have been suggested. To test some of these theories, we re-analyzed data from Bonnevie et al., 2013, in which the hippocampus was inactivated and grid cells were recorded in the rat MEC. We investigated whether the firing associations of grid cells depend on hippocampal inputs. Specifically, we examined temporal and spatial correlations in the firing times of simultaneously recorded grid cells before and during hippocampal inactivation. Our analysis revealed evidence of network coherence in grid cells even in the absence of hippocampal input to the MEC, both in regular grid cells and in those that became head-direction cells after hippocampal inactivation. This favors models, which suggest that phase relations between grid cells in the MEC are dependent on intrinsic connectivity within the MEC.

The Subthalamic Nucleus: Unravelling New Roles and Mechanisms in the Control of Action.

How do we decide what we do? This is the essence of action control, the process of selecting the most appropriate response among multiple possible choices. Suboptimal action control can involve a failure to initiate or adapt actions, or conversely it can involve making actions impulsively. There has been an increasing focus on the specific role of the subthalamic nucleus (STN) in action control. This has been fueled by the clinical relevance of this basal ganglia nucleus as a target for deep brain stimulation (DBS), primarily in Parkinson's disease but also in obsessive-compulsive disorder. The context of DBS has opened windows to study STN function in ways that link neuroscientific and clinical fields closely together, contributing to an exceptionally high level of two-way translation. In this review, we first outline the role of the STN in both motor and nonmotor action control, and then discuss how these functions might be implemented by neuronal activity in the STN. Gaining a better understanding of these topics will not only provide important insights into the neurophysiology of action control but also the pathophysiological mechanisms relevant for several brain disorders and their therapies.

Topography of head direction cells in medial entorhinal cortex.

BACKGROUND: Neural circuits in the medial entorhinal cortex (MEC) support translation of the external environment to an internal map of space, with grid and head direction neurons providing metrics for distance and orientation. RESULTS: We show here that head direction cells in MEC are organized topographically. Head direction tuning varies widely across the entire dorsoventral MEC axis, but in layer III there is a gradual dorsal-to-ventral increase in the average width of the directional firing field. Sharply tuned cells were encountered only at the dorsal end of MEC. Similar topography was not observed among head direction cells in layers V-VI. At all MEC locations, in all layers, the preferred firing direction (directional phase) showed a uniform distribution. The continuity of the dorsoventral tuning gradient coexisted with discrete topography in the spatial scale of simultaneously recorded grid cells. CONCLUSIONS: The findings point to dorsoventral gradients as a fundamental property of entorhinal circuits, upon which modular organization may be expressed in select subpopulations.

Grid cells require excitatory drive from the hippocampus.

To determine how hippocampal backprojections influence spatially periodic firing in grid cells, we recorded neural activity in the medial entorhinal cortex (MEC) of rats after temporary inactivation of the hippocampus. We report two major changes in entorhinal grid cells. First, hippocampal inactivation gradually and selectively extinguished the grid pattern. Second, the same grid cells that lost their grid fields acquired substantial tuning to the direction of the rat's head. This transition in firing properties was contingent on a drop in the average firing rate of the grid cells and could be replicated by the removal of an external excitatory drive in an attractor network model in which grid structure emerges by velocity-dependent translation of activity across a network with inhibitory connections. These results point to excitatory drive from the hippocampus, and possibly other regions, as one prerequisite for the formation and translocation of grid patterns in the MEC.

Frequency of gamma oscillations routes flow of information in the hippocampus.

Gamma oscillations are thought to transiently link distributed cell assemblies that are processing related information, a function that is probably important for network processes such as perception, attentional selection and memory. This 'binding' mechanism requires that spatially distributed cells fire together with millisecond range precision; however, it is not clear how such coordinated timing is achieved given that the frequency of gamma oscillations varies substantially across space and time, from approximately 25 to almost 150 Hz. Here we show that gamma oscillations in the CA1 area of the hippocampus split into distinct fast and slow frequency components that differentially couple CA1 to inputs from the medial entorhinal cortex, an area that provides information about the animal's current position, and CA3, a hippocampal subfield essential for storage of such information. Fast gamma oscillations in CA1 were synchronized with fast gamma in medial entorhinal cortex, and slow gamma oscillations in CA1 were coherent with slow gamma in CA3. Significant proportions of cells in medial entorhinal cortex and CA3 were phase-locked to fast and slow CA1 gamma waves, respectively. The two types of gamma occurred at different phases of the CA1 theta rhythm and mostly on different theta cycles. These results point to routeing of information as a possible function of gamma frequency variations in the brain and provide a mechanism for temporal segregation of potentially interfering information from different sources.

Hippocampus-independent phase precession in entorhinal grid cells.

Theta-phase precession in hippocampal place cells is one of the best-studied experimental models of temporal coding in the brain. Theta-phase precession is a change in spike timing in which the place cell fires at progressively earlier phases of the extracellular theta rhythm as the animal crosses the spatially restricted firing field of the neuron. Within individual theta cycles, this phase advance results in a compressed replication of the firing sequence of consecutively activated place cells along the animal's trajectory, at a timescale short enough to enable spike-time-dependent plasticity between neurons in different parts of the sequence. The neuronal circuitry required for phase precession has not yet been established. The fact that phase precession can be seen in hippocampal output stuctures such as the prefrontal cortex suggests either that efferent structures inherit the precession from the hippocampus or that it is generated locally in those structures. Here we show that phase precession is expressed independently of the hippocampus in spatially modulated grid cells in layer II of medial entorhinal cortex, one synapse upstream of the hippocampus. Phase precession is apparent in nearly all principal cells in layer II but only sparsely in layer III. The precession in layer II is not blocked by inactivation of the hippocampus, suggesting that the phase advance is generated in the grid cell network. The results point to possible mechanisms for grid formation and raise the possibility that hippocampal phase precession is inherited from entorhinal cortex.