ABSTRACT
A new study identifies representations of navigational variables in six prefrontal regions in freely moving macaques, expanding our view of how the brain represents space outside of the broader hippocampal formation.
Subject(s)
Cognition , Prefrontal Cortex , Animals , Brain , Hippocampus , MacacaABSTRACT
As the old adage goes: practice makes perfect. Yet, the neural mechanisms by which rote repetition transforms a halting behavior into a fluid, effortless, and "automatic" action are not well understood. Here we consider the possibility that well-practiced motor sequences, which initially rely on higher-level decision-making circuits, become wholly specified in lower-level control circuits. We review studies informing this idea, discuss the constraints on such shift in control, and suggest approaches to pinpoint circuit-level changes associated with motor sequence learning.
Subject(s)
LearningABSTRACT
Neural circuits generate representations of the external world from multiple information streams. The navigation system provides an exceptional lens through which we may gain insights about how such computations are implemented. Neural circuits in the medial temporal lobe construct a map-like representation of space that supports navigation. This computation integrates multiple sensory cues, and, in addition, is thought to require cues related to the individual's movement through the environment. Here, we identify multiple self-motion signals, related to the position and velocity of the head and eyes, encoded by neurons in a key node of the navigation circuitry of mice, the medial entorhinal cortex (MEC). The representation of these signals is highly integrated with other cues in individual neurons. Such information could be used to compute the allocentric location of landmarks from visual cues and to generate internal representations of space.
Subject(s)
Entorhinal Cortex/physiology , Nerve Net/physiology , Neurons/physiology , Spatial Navigation/physiology , Visual Perception/physiology , Algorithms , Animals , Cues , Entorhinal Cortex/cytology , Eye Movements/physiology , Female , Head Movements/physiology , Male , Mice, 129 Strain , Mice, Inbred C57BL , Models, Neurological , Nerve Net/cytologyABSTRACT
Medial entorhinal cortex contains neural substrates for representing space. These substrates include grid cells that fire in repeating locations and increase in scale progressively along the dorsal-to-ventral entorhinal axis, with the physical distance between grid firing nodes increasing from tens of centimeters to several meters in rodents. Whether the temporal scale of grid cell spiking dynamics shows a similar dorsal-to-ventral organization remains unknown. Here, we report the presence of a dorsal-to-ventral gradient in the temporal spiking dynamics of grid cells in behaving mice. This gradient in bursting supports the emergence of a dorsal grid cell population with a high signal-to-noise ratio. In vitro recordings combined with a computational model point to a role for gradients in non-inactivating sodium conductances in supporting the bursting gradient in vivo. Taken together, these results reveal a complementary organization in the temporal and intrinsic properties of entorhinal cells.
Subject(s)
Entorhinal Cortex/metabolism , Neurons/metabolism , Topography, Medical/methods , Animals , Female , Male , Mice , Models, NeurologicalABSTRACT
The entorhinal cortex contains neurons that represent self-location, including grid cells that fire in periodic locations and velocity signals that encode running speed and head direction. Although the size and shape of the environment influence grid patterns, whether entorhinal velocity signals are equally influenced or provide a universal metric for self-motion across environments remains unknown. Here we report that speed cells rescale after changes to the size and shape of the environment. Moreover, head direction cells reorganize in an experience-dependent manner to align with the axis of environmental change. A knockout mouse model allows dissociation of the coordination between cell types, with grid and speed cells, but not head direction cells, responding in concert to environmental change. These results point to malleability in the coding features of multiple entorhinal cell types and have implications for which cell types contribute to the velocity signal used by computational models of grid cells.
Subject(s)
Entorhinal Cortex/physiology , Grid Cells/physiology , Models, Neurological , Space Perception/physiology , Spatial Navigation/physiology , Animals , Computer Simulation , Male , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
In this issue of Neuron, a new study by Minderer et al. (2019) examines the activity of thousands of cortical neurons during a navigation task and reveals that features of the task encoded by neurons vary smoothly across cortex rather than falling into functionally discrete cortical regions.
Subject(s)
Neurons , Animals , MiceABSTRACT
Ethologically relevant navigational strategies often incorporate remembered reward locations. Although neurons in the medial entorhinal cortex provide a maplike representation of the external spatial world, whether this map integrates information regarding learned reward locations remains unknown. We compared entorhinal coding in rats during a free-foraging task and a spatial memory task. Entorhinal spatial maps restructured to incorporate a learned reward location, which in turn improved positional decoding near this location. This finding indicates that different navigational strategies drive the emergence of discrete entorhinal maps of space and points to a role for entorhinal codes in a diverse range of navigational behaviors.
Subject(s)
Entorhinal Cortex/physiology , Grid Cells/physiology , Mental Recall/physiology , Reward , Spatial Navigation/physiology , Animals , Brain Mapping , Entorhinal Cortex/cytology , Head Movements , Male , RatsABSTRACT
Upon encountering a novel environment, an animal must construct a consistent environmental map, as well as an internal estimate of its position within that map, by combining information from two distinct sources: self-motion cues and sensory landmark cues. How do known aspects of neural circuit dynamics and synaptic plasticity conspire to accomplish this feat? Here we show analytically how a neural attractor model that combines path integration of self-motion cues with Hebbian plasticity in synaptic weights from landmark cells can self-organize a consistent map of space as the animal explores an environment. Intriguingly, the emergence of this map can be understood as an elastic relaxation process between landmark cells mediated by the attractor network. Moreover, our model makes several experimentally testable predictions, including (i) systematic path-dependent shifts in the firing fields of grid cells toward the most recently encountered landmark, even in a fully learned environment; (ii) systematic deformations in the firing fields of grid cells in irregular environments, akin to elastic deformations of solids forced into irregular containers; and (iii) the creation of topological defects in grid cell firing patterns through specific environmental manipulations. Taken together, our results conceptually link known aspects of neurons and synapses to an emergent solution of a fundamental computational problem in navigation, while providing a unified account of disparate experimental observations.
Subject(s)
Exploratory Behavior/physiology , Models, Neurological , Space Perception/physiology , Animals , Biophysical Phenomena , Elasticity , Entorhinal Cortex/cytology , Entorhinal Cortex/physiology , Feedback, Sensory/physiology , Learning/physiology , Nerve Net/cytology , Nerve Net/physiology , Neuronal Plasticity , Neurons/physiologyABSTRACT
Medial entorhinal cortex (MEC) grid cells fire at regular spatial intervals and project to the hippocampus, where place cells are active in spatially restricted locations. One feature of the grid population is the increase in grid spatial scale along the dorsal-ventral MEC axis. However, the difficulty in perturbing grid scale without impacting the properties of other functionally defined MEC cell types has obscured how grid scale influences hippocampal coding and spatial memory. Here we use a targeted viral approach to knock out HCN1 channels selectively in MEC, causing the grid scale to expand while leaving other MEC spatial and velocity signals intact. Grid scale expansion resulted in place scale expansion in fields located far from environmental boundaries, reduced long-term place field stability and impaired spatial learning. These observations, combined with simulations of a grid-to-place cell model and position decoding of place cells, illuminate how grid scale impacts place coding and spatial memory.
Subject(s)
Brain Mapping , Entorhinal Cortex/cytology , Grid Cells/physiology , Neural Pathways/physiology , Place Cells/physiology , Space Perception/physiology , Action Potentials/genetics , Action Potentials/physiology , Animals , Animals, Newborn , Electroencephalography , Female , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Hippocampus/cytology , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/deficiency , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Neurological , Phosphopyruvate Hydratase/metabolism , Potassium Channels/deficiency , Potassium Channels/geneticsABSTRACT
Technological advances in profiling cells along genetic, anatomical and physiological axes have fomented interest in identifying all neuronal cell types. This goal nears completion in specialized circuits such as the retina, while remaining more elusive in higher order cortical regions. We propose that this differential success of cell type identification may not simply reflect technological gaps in co-registering genetic, anatomical and physiological features in the cortex. Rather, we hypothesize it reflects evolutionarily driven differences in the computational principles governing specialized circuits versus more general-purpose learning machines. In this framework, we consider the question of cell types in medial entorhinal cortex (MEC), a region likely to be involved in memory and navigation. While MEC contains subsets of identifiable functionally defined cell types, recent work employing unbiased statistical methods and more diverse tasks reveals unsuspected heterogeneity and adaptivity in MEC firing patterns. This suggests MEC may operate more as a generalist circuit, obeying computational design principles resembling those governing other higher cortical regions.
Subject(s)
Entorhinal Cortex/cytology , Nerve Net/physiology , Neurons/physiology , Space Perception/physiology , Action Potentials/physiology , Animals , Entorhinal Cortex/physiology , HumansABSTRACT
Medial entorhinal grid cells display strikingly symmetric spatial firing patterns. The clarity of these patterns motivated the use of specific activity pattern shapes to classify entorhinal cell types. While this approach successfully revealed cells that encode boundaries, head direction, and running speed, it left a majority of cells unclassified, and its pre-defined nature may have missed unconventional, yet important coding properties. Here, we apply an unbiased statistical approach to search for cells that encode navigationally relevant variables. This approach successfully classifies the majority of entorhinal cells and reveals unsuspected entorhinal coding principles. First, we find a high degree of mixed selectivity and heterogeneity in superficial entorhinal neurons. Second, we discover a dynamic and remarkably adaptive code for space that enables entorhinal cells to rapidly encode navigational information accurately at high running speeds. Combined, these observations advance our current understanding of the mechanistic origins and functional implications of the entorhinal code for navigation. VIDEO ABSTRACT.
Subject(s)
Action Potentials/physiology , Entorhinal Cortex/physiology , Neurons/physiology , Space Perception/physiology , Theta Rhythm/physiology , Animals , Female , Head , Male , Mice, Inbred C57BL , Models, Neurological , Motor Activity/physiologyABSTRACT
Previous studies have demonstrated that mean activity levels in the hippocampus oscillate on a circadian timescale, both at the single neuron and EEG level. This oscillation is also entrained by the availability of food, suggesting that the circadian modulation of hippocampal activity might comprise part of the recently discovered food-entrainable circadian oscillator (FEO). In order to determine whether the circadian oscillation in hippocampal activity is linked to activity in other brain regions, we recorded field-potential EEG from hippocampus and two cortical regions known to connect to hippocampus; the anterior cingulate cortex and the agranular insular cortex. These latter regions are involved in executive control (cingulate) and gustatory feedback (insula) and so are in a position where they could usefully contribute to, or benefit from, hippocampal memorial information in order to undertake task-related processing. We recorded EEG from these three regions for 20 m every hour for 58 consecutive hours in one continuous exposure to the recording environment. We found that there are regular and distinct increases in magnitude coherence between hippocampus and both cortical regions for EEG in both theta (6-12 Hz) and gamma (30-48 Hz) bands. These periods of increased coherence are spaced approximately one solar day apart, appear not to be specifically light-entrained, and are most apparent for gamma frequency activity. The gamma association between the two cortical regions shows the same temporal pattern of coherence peaks as the hippocampal-cortical coherences. We propose that these peaks in coherence represent the transient synchronization of temporally tagged memorial information between the hippocampus and other brain regions for which this information may be relevant. These findings suggest that the FEO involves coordinated activity across a number of brain regions and may underlie a mechanism via which an organism can store and recall salient gustatory events on a circadian timescale.
ABSTRACT
We present a population density and moment-based description of the stochastic dynamics of domain [Formula: see text]-mediated inactivation of L-type [Formula: see text] channels. Our approach accounts for the effect of heterogeneity of local [Formula: see text] signals on whole cell [Formula: see text] currents; however, in contrast with prior work, e.g., Sherman et al. (Biophys J 58(4):985-995, 1990), we do not assume that [Formula: see text] domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain model of an L-type [Formula: see text] channel introduced by Greenstein and Winslow (Biophys J 83(6):2918-2945, 2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell [Formula: see text] current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of [Formula: see text] inactivation that may occur via slow heterogeneous domain [[Formula: see text]]. Next, we find that when channel permeability is held constant, [Formula: see text]-mediated inactivation of L-type channels increases as the domain time constant increases, because a slow domain collapse rate leads to increased mean domain [[Formula: see text]] near open channels; conversely, when the maximum domain [[Formula: see text]] is held constant, inactivation decreases as the domain time constant increases. Comparison of simulation results using population densities and moment equations confirms the computational efficiency of the moment-based approach, and enables the validation of two distinct methods of truncating and closing the open system of moment equations. In general, a slow domain time constant requires higher order moment truncation for agreement between moment-based and population density simulations.
Subject(s)
Calcium Channels, L-Type/metabolism , Calcium/metabolism , Models, Theoretical , Population Density , Algorithms , Humans , Markov ChainsABSTRACT
Medial entorhinal grid cells fire in periodic, hexagonally patterned locations and are proposed to support path-integration-based navigation. The recursive nature of path integration results in accumulating error and, without a corrective mechanism, a breakdown in the calculation of location. The observed long-term stability of grid patterns necessitates that the system either performs highly precise internal path integration or implements an external landmark-based error correction mechanism. To distinguish these possibilities, we examined grid cells in behaving rodents as they made long trajectories across an open arena. We found that error accumulates relative to time and distance traveled since the animal last encountered a boundary. This error reflects coherent drift in the grid pattern. Further, interactions with boundaries yield direction-dependent error correction, suggesting that border cells serve as a neural substrate for error correction. These observations, combined with simulations of an attractor network grid cell model, demonstrate that landmarks are crucial to grid stability.
Subject(s)
Action Potentials/physiology , Entorhinal Cortex/cytology , Environment , Models, Neurological , Neurons/physiology , Animals , Computer Simulation , Datasets as Topic , Exploratory Behavior/physiology , Mice , Nerve Net/physiology , Probability , Space Perception/physiology , Time FactorsABSTRACT
While the research programs in early cognitive science and artificial intelligence aimed to articulate what cognition was in ideal terms, much research in contemporary computational neuroscience looks at how and why brains fail to function as they should ideally. This focus on impairment affects how we understand David Marr's hypothesized three levels of understanding. In this essay, we suggest some refinements to Marr's distinctions using a population activity model of cortico-striatal circuitry exploring impulsivity and behavioral inhibition as a case study. In particular, we urge that Marr's computational level should be redefined to include a description of how systems break down. We also underscore that feed-forward processing, cognition disconnected from behavioral context, and representations do not always drive cognition in the way that Marr originally assumed.