Unweaving the Cognitive Map: A Personal History.

I have been incredibly fortunate to have worked in the field of hippocampal spatial coding during three of its most exciting decades, the 1990s, 2000s, and 2010s. During this time I had a ringside view of some of the foundational discoveries that were made which have transformed our understanding of the hippocampal system and its role in cognition (especially spatial cognition) and memory. These discoveries inspired me in my own lab over the years to pursue three broad lines of enquiry-3D spatial encoding, context and the sense of direction-which are outlined here.

The dorsal thalamic lateral geniculate nucleus is required for visual control of head direction cell firing direction in rats.

Head direction (HD) neurons, signalling facing direction, generate a signal that is primarily anchored to the outside world by visual inputs. We investigated the route for visual landmark information into the HD system in rats. There are two candidates: an evolutionarily older, larger subcortical retino-tectal pathway and a more recently evolved, smaller cortical retino-geniculo-striate pathway.

Unpacking the navigation toolbox: insights from comparative cognition.

The study of navigation is informed by ethological data from many species, laboratory investigation at behavioural and neurobiological levels, and computational modelling. However, the data are often species-specific, making it challenging to develop general models of how biology supports behaviour. Wiener .

The mosaic structure of the mammalian cognitive map.

The cognitive map, proposed by Tolman in the 1940s, is a hypothetical internal representation of space constructed by the brain to enable an animal to undertake flexible spatial behaviors such as navigation. The subsequent discovery of place cells in the hippocampus of rats suggested that such a map-like representation does exist, and also provided a tool with which to explore its properties. Single-neuron studies in rodents conducted in small singular spaces have suggested that the map is founded on a metric framework, preserving distances and directions in an abstract representational format.

A configural context signal simultaneously but separably drives positioning and orientation of hippocampal place fields.

Effective self-localization requires that the brain can resolve ambiguities in incoming sensory information arising from self-similarities (symmetries) in the environment structure. We investigated how place cells use environmental cues to resolve the ambiguity of a rotationally symmetric environment, by recording from hippocampal CA1 in rats exploring a "2-box." This apparatus comprises two adjacent rectangular compartments, identical but with directionally opposed layouts (cue card at one end and central connecting doorway) and distinguished by their odor contexts (lemon vs.

Convergence of location, direction, and theta in the rat anteroventral thalamic nucleus.

The thalamus and cortex are anatomically interconnected, with the thalamus providing integral information for cortical functions. The anteroventral thalamic nucleus (AV) is reciprocally connected to retrosplenial cortex (RSC). Two distinct AV subfields, dorsomedial (AVDM) and ventrolateral (AVVL), project differentially to granular vs.

Symmetries and asymmetries in the neural encoding of 3D space.

The neural coding of space centres on three foundational cell types: place cells, head direction cells and grid cells. One notable characteristic of these neurons is the symmetry properties of their spatial firing patterns. In symmetric environments, firing patterns are often also symmetric: for example, place cells show translational symmetry in aligned sub-compartments of a multi-compartment environment.

Environment Symmetry Drives a Multidirectional Code in Rat Retrosplenial Cortex.

We investigated how environment symmetry shapes the neural processing of direction by recording directionally tuned retrosplenial neurons in male Lister hooded rats exploring multicompartment environments that had different levels of global rotational symmetry. Our hypothesis built on prior observations of twofold symmetry in the directional tuning curves of rats in a globally twofold-symmetric environment. To test whether environment symmetry was the relevant factor shaping the directional responses, here we deployed the same apparatus (two connected rectangular boxes) plus one with fourfold symmetry (a 2 × 2 array of connected square boxes) and one with onefold symmetry (a circular open-field arena).

Climate crisis and ecological emergency: Why they concern (neuro)scientists, and what we can do.

Our planet is experiencing severe and accelerating climate and ecological breakdown caused by human activity. As professional scientists, we are better placed than most to understand the data that evidence this fact. However, like most other people, we ignore this inconvenient truth and lead our daily lives, at home and at work, as if these facts weren't true.

Evidence for two distinct thalamocortical circuits in retrosplenial cortex.

Retrosplenial cortex (RSC) lies at the interface between sensory and cognitive networks in the brain and mediates between these, although it is not yet known how. It has two distinct subregions, granular (gRSC) and dysgranular (dRSC). The present study investigated how these subregions differ with respect to their electrophysiology and thalamic connectivity, as a step towards understanding their functions.

Irregular distribution of grid cell firing fields in rats exploring a 3D volumetric space.

We investigated how entorhinal grid cells encode volumetric space. On a horizontal surface, grid cells usually produce multiple, spatially focal, approximately circular firing fields that are evenly sized and spaced to form a regular, close-packed, hexagonal array. This spatial regularity has been suggested to underlie navigational computations.

How environmental movement constraints shape the neural code for space.

Study of the neural code for space in rodents has many insights to offer for how mammals, including humans, construct a mental representation of space. This code is centered on the hippocampal place cells, which are active in particular places in the environment. Place cells are informed by numerous other spatial cell types including grid cells, which provide a signal for distance and direction and are thought to help anchor the place cell signal.

Hippocampal place cells encode global location but not connectivity in a complex space.

Flexible navigation relies on a cognitive map of space, thought to be implemented by hippocampal place cells: neurons that exhibit location-specific firing. In connected environments, optimal navigation requires keeping track of one's location and of the available connections between subspaces. We examined whether the dorsal CA1 place cells of rats encode environmental connectivity in four geometrically identical boxes arranged in a square.

Transitions in Brain Evolution: Space, Time and Entropy.

How did brains evolve to become so complex, and what is their future? Brains pose an explanatory challenge because entropy, which inexorably increases over time, is commonly associated with disorder and simplicity. Recently we showed how evolution is an entropic process, building structures - organisms - which themselves facilitate entropy growth. Here we suggest that key transitional points in evolution extended organisms' reach into space and time, opening channels into new regions of a complex multidimensional state space that also allow entropy to increase.

How Can Neuroscientists Respond to the Climate Emergency?

The world faces a climate emergency. Here, we consider the actions that can be taken by neuroscientists to tackle climate change. We encourage neuroscientists to put emissions reductions at the center of their everyday professional activities.

The place-cell representation of volumetric space in rats.

Place cells are spatially modulated neurons found in the hippocampus that underlie spatial memory and navigation: how these neurons represent 3D space is crucial for a full understanding of spatial cognition. We wirelessly recorded place cells in rats as they explored a cubic lattice climbing frame which could be aligned or tilted with respect to gravity. Place cells represented the entire volume of the mazes: their activity tended to be aligned with the maze axes, and when it was more difficult for the animals to move vertically the cells represented space less accurately and less stably.

Insensitivity of Place Cells to the Value of Spatial Goals in a Two-Choice Flexible Navigation Task.

Hippocampal place cells show position-specific activity thought to reflect a self-localization signal. Several reports also point to some form of goal encoding by place cells. We investigated this by asking whether they also encode the value of spatial goals, which is crucial information for optimizing goal-directed navigation.

Cognitive representations of spatial location.

Spatial memory has fascinated psychologists ever since the discipline began, but a series of findings beginning in the middle of last century propelled its study into the domain of neuroscience and helped bring about the cognitive revolution in psychology. Starting with the discovery that the hippocampus plays a central role in memory, particularly spatial memory, studies of the mammalian hippocampus and related regions over the latter half of the century slowly uncovered an extensive neural system involved in processing place, head direction, objects, speed and other spatially informative parameters. Meanwhile, the concurrent discovery of hippocampal synaptic plasticity allowed theoreticians and experimentalists to collaborate in linking spatial perception and memory, and genetic techniques developed towards the end of the century opened the door to circuit dissections of these processes.

Landmark-Based Updating of the Head Direction System by Retrosplenial Cortex: A Computational Model.

Maintaining a sense of direction is fundamental to navigation, and is achieved in the brain by a network of head direction (HD) cells, which update their signal using stable environmental landmarks. How landmarks are detected and their stability determined is still unknown. Recently we reported a new class of cells (Jacob et al.

The Hippocampus: From Memory, to Map, to Memory Map.

The hippocampus is one of the brain's great mysteries. Historically, theories of its function included emotion, response inhibition, general memory and spatial perception/learning, with memory versus space emerging as a particular focus of more recent debates. A 1978 paper by Olton and colleagues captured this dichotomy by exploiting their newly developed radial maze task to reveal a profound deficit in the ability of hippocampally lesioned rats to execute a spatial memory task.

A dual-axis rotation rule for updating the head direction cell reference frame during movement in three dimensions.

In the mammalian brain, allocentric (Earth-referenced) head direction, called azimuth, is encoded by head direction (HD) cells, which fire according to the facing direction of the animal's head. On a horizontal surface, rotations of the head around the dorsoventral (D-V) axis, called yaw, correspond to changes in azimuth and elicit appropriate updating of the HD "compass" signal to enable large-scale navigation. However, if the animal moves through three-dimensional (3D) space then there is no longer a simple relationship between yaw rotations and azimuth changes, and so processing of 3D rotations is needed.

Multivoxel Pattern Analysis Reveals 3D Place Information in the Human Hippocampus.

The spatial world is three dimensional (3D) and humans and other animals move both horizontally and vertically within it. Extant neuroscientific studies have typically investigated spatial navigation on a horizontal 2D plane, leaving much unknown about how 3D spatial information is represented in the brain. Specifically, horizontal and vertical information may be encoded in the same or different neural structures with equal or unequal sensitivity.

The representation of space in the brain.

Animals can navigate vast distances and often display behaviours or activities that indicate a detailed, internal spatial representation of their surrounding environment or a 'cognitive map'. Over a century of behavioural research on spatial navigation in humans and animals has greatly increased our understanding of how this highly complex feat is achieved. In turn this has inspired half a century of electrophysiological spatial navigation and memory research which has further advanced our understanding of the brain.