Dori Derdikman

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 rats 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.

Fragmentation of grid cell maps in a multicompartment environment

To determine whether entorhinal spatial representations are continuous or fragmented, we recorded neural activity in grid cells while rats ran through a stack of interconnected, zig-zagged compartments of equal shape and orientation (a hairpin maze). The distribution of spatial firing fields was markedly similar across all compartments in which running occurred in the same direction, implying that the grid representation was fragmented into repeating submaps. Activity at neighboring positions was least correlated at the transitions between different arms, indicating that the map split regularly at the turning points. We saw similar discontinuities among place cells in the hippocampus. No fragmentation was observed when the rats followed similar trajectories in the absence of internal walls, implying that stereotypic behavior alone cannot explain the compartmentalization. These results indicate that spatial environments are represented in entorhinal cortex and hippocampus as a mosaic of discrete submaps that correspond to the geometric structure of the space.

A manifold of spatial maps in the brain

Two neural systems are known to encode self-location in the brain: Place cells in the hippocampus encode unique locations in unique environments, whereas grid cells, border cells and head-direction cells in the parahippocampal cortex provide a universal metric for mapping positions and directions in all environments. These systems have traditionally been studied in very simple environments; however, natural environments are compartmentalized, nested and variable in time. Recent studies indicate that hippocampal and entorhinal spatial maps reflect this complexity. The maps fragment into interconnected, rapidly changing and tightly coordinated submaps. Plurality, fast dynamics and dynamic grouping are optimal for a brain system thought to exploit large pools of stored information to guide behavior on a second-by-second time frame in the animals natural habitat.

Three-dimensional head-direction coding in the bat brain

Navigation requires a sense of direction (‘compass’), which in mammals is thought to be provided by head-direction cells, neurons that discharge when the animal’s head points to a specific azimuth. However, it remains unclear whether a three-dimensional (3D) compass exists in the brain. Here we conducted neural recordings in bats, mammals well-adapted to 3D spatial behaviours, and found head-direction cells tuned to azimuth, pitch or roll, or to conjunctive combinations of 3D angles, in both crawling and flying bats. Head-direction cells were organized along a functional–anatomical gradient in the presubiculum, transitioning from 2D to 3D representations. In inverted bats, the azimuth-tuning of neurons shifted by 180°, suggesting that 3D head direction is represented in azimuth × pitch toroidal coordinates. Consistent with our toroidal model, pitch-cell tuning was unimodal, circular, and continuous within the available 360° of pitch. Taken together, these results demonstrate a 3D head-direction mechanism in mammals, which could support navigation in 3D space.

Pre-neuronal morphological processing of object location by individual whiskers

In the vibrissal system, touch information is conveyed by a receptorless whisker hair to follicle mechanoreceptors, which then provide input to the brain. We examined whether any processing, that is, meaningful transformation, occurs in the whisker itself. Using high-speed videography and tracking the movements of whiskers in anesthetized and behaving rats, we found that whisker-related morphological phase planes, based on angular and curvature variables, can represent the coordinates of object position after contact in a reliable manner, consistent with theoretical predictions. By tracking exposed follicles, we found that the follicle-whisker junction is rigid, which enables direct readout of whisker morphological coding by mechanoreceptors. Finally, we found that our behaving rats pushed their whiskers against objects during localization in a way that induced meaningful morphological coding and, in parallel, improved their localization performance, which suggests a role for pre-neuronal morphological computation in active vibrissal touch.

Space, time and memory in the hippocampal formation

In primates as well as rodents, the posterior parietal cortex maps spatial relationships having both egocentric and external frames of reference. In this chapter, the form in which rat posterior parietal cortex neuronal activity maps position within trajectories through the environment is considered in detail and compared to the forms of spatial mapping observed for neurons of the hippocampus and entorhinal cortex. Evidence is presented to indicate that posterior parietal neurons simultaneously map positions both within and across segments of paths through an environment. It is suggested that the specific nature of posterior parietal cortex mapping of space serves, in part, to transition knowledge of position in the environment, given by hippocampus and entorhinal cortex, into efficient path-running behavior via projections to primary and secondary sensory and motor cortices. Posterior parietal cortex activity is also hypothesized to play a role both in driving trajectory dependence of hippocampal place cells and in anchoring spatially specific hippocampal and entorhinal cortical activity to the boundaries of the observable environment.

Coding of Object Location in the Vibrissal Thalamocortical System

In whisking rodents, object location is encoded at the receptor level by a combination of motor and sensory related signals. Recoding of the encoded signals can result in various forms of internal representations. Here, we examined the coding schemes occurring at the first forebrain level that receives inputs necessary for generating such internal representations--the thalamocortical network. Single units were recorded in 8 thalamic and cortical stations in artificially whisking anesthetized rats. Neuronal representations of object location generated across these stations and expressed in response latency and magnitude were classified based on graded and binary coding schemes. Both graded and binary coding schemes occurred across the entire thalamocortical network, with a general tendency of graded-to-binary transformation from thalamus to cortex. Overall, 63% of the neurons of the thalamocortical network coded object position in their firing. Thalamocortical responses exhibited a slow dynamics during which the amount of coded information increased across 4-5 whisking cycles and then stabilized. Taken together, the results indicate that the thalamocortical network contains dynamic mechanisms that can converge over time on multiple coding schemes of object location, schemes which essentially transform temporal coding to rate coding and gradual to labeled-line coding.

Grid cells correlation structure suggests organized feedforward projections into superficial layers of the medial entorhinal cortex

Navigation requires integration of external and internal inputs to form a representation of location. Part of this integration is considered to be carried out by the grid cells network in the medial entorhinal cortex (MEC). However, the structure of this neural network is unknown. To shed light on this structure, we measured noise correlations between 508 pairs of simultaneous previously recorded grid cells. We differentiated between pure grid and conjunctive cells (pure grid in Layers II, III, and VI vs. conjunctive in Layers III and V—only Layer III was bi‐modal), and devised a new method to classify cell pairs as belonging/not‐belonging to the same module. We found that pairs from the same module show significantly more correlations than pairs from different modules. The correlations between pure grid cells decreased in strength as their relative spatial phase increased. However, correlations were mostly at 0 time‐lag, suggesting that the source of correlations was not only synaptic, but rather resulted mostly from common input. Given our measured correlations, the two functional groups of grid cells (pure vs. conjunctive), and the known disorganized recurrent connections within Layer II, we propose the following model: conjunctive cells in deep layers form an attractor network whose activity is governed by velocity‐controlled signals. A second manifold in Layer II receives organized feedforward projections from the deep layers, giving rise to pure grid cells. Numerical simulations indicate that organized projections induce such correlations as we measure in superficial layers. Our results provide new evidence for the functional anatomy of the entorhinal circuit—suggesting that strong phase‐organized feedforward projections support grid fields in the superficial layers.

A Dual Role for Hippocampal Replay

Hippocampal place cells are active when the rat is at certain locations. The sequence of these active place cells is known to be rapidly replayed during sharp-wave-ripple events in the EEG. In this issue of Neuron, a study by Gupta et al. challenges previous notions that the replayed trajectories are solely a passive echo of past episodes. Rather, replay might also be an active process constructing a Tolmanian cognitive map of space, which makes flexible navigation possible.

Head direction maps remain stable despite grid map fragmentation

Areas encoding space in the brain contain both representations of position (place cells and grid cells) and representations of azimuth (head direction cells). Previous studies have already suggested that although grid cells and head direction cells reside in the same brain areas, the calculation of head direction is not dependent on the calculation of position. Here we demonstrate that realignment of grid cells does not affect head direction tuning. We analyzed head direction cell data collected while rats performed a foraging task in a multi-compartment environment (the hairpin maze) vs. an open-field environment, demonstrating that the tuning of head direction cells did not change when the environment was divided into multiple sub-compartments, in the hairpin maze. On the other hand, as we have shown previously (Derdikman et al., 2009), the hexagonal firing pattern expressed by grid cells in the open-field broke down into repeating patterns in similar alleys when rats traversed the multi-compartment hairpin maze. The grid-like firing of conjunctive cells, which express both grid properties and head direction properties in the open-field, showed a selective fragmentation of grid-like firing properties in the hairpin maze, while the head directionality property of the same cells remained unaltered. These findings demonstrate that head direction is not affected during the restructuring of grid cell firing fields as a rat actively moves between compartments, thus strengthening the claim that the head direction system is upstream from or parallel to the grid-place system.