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James J Knierim

Publications and source records attributed to James J Knierim.

13 recordsLinked to original sources

Backward shift of head direction tuning curves of the anterior thalamus: comparison with CA1 place fields.

The head direction cell system is composed of multiple regions associated with the hippocampal formation. The dynamics of head direction tuning curves (HDTCs) were compared with those of hippocampal place fields. In both familiar and cue-altered environments, as a rat ran an increasing number of laps on a track, the center of mass (COM) of the HDTC tended to shift backward, similar to shifting observed in place cells. However, important differences existed between these cells in terms of the shift patterns relative to the cue-altered conditions, the proportion of backward versus forward shifts, and the time course of shift resetting. The demonstration of backward COM shifts in head direction cells and place cells suggests that similar plasticity mechanisms (such as temporally asymmetric LTP induction or spike timing-dependent plasticity) may be at work in both brain systems, and these processes may reflect a general mechanism for storing learned sequences of neural activity patterns.

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Head direction cell representations maintain internal coherence during conflicting proximal and distal cue rotations: comparison with hippocampal place cells.

Place cells of the hippocampal formation encode a spatial representation of the environment, and the orientation of this representation is apparently governed by the head direction cell system. The representation of a well explored environment by CA1 place cells can be split when there is conflicting information from salient proximal and distal cues, because some place fields rotate to follow the distal cues, whereas others rotate to follow the proximal cues (Knierim, 2002a). In contrast, the CA3 representation is more coherent than CA1, because the place fields in CA3 tend to rotate in the same direction (Lee et al., 2004). The present study tests whether the head direction cell network produces a split representation or remains coherent under these conditions by simultaneously recording both CA1 place cells and head direction cells from the thalamus. In agreement with previous studies, split representations of the environment were observed in ensembles of CA1 place cells in approximately 75% of the mismatch sessions, in which some fields followed the counterclockwise rotation of proximal cues and other fields followed the clockwise rotation of distal cues. However, of 225 recording sessions, there was not a single instance of the head direction cell ensembles revealing a split representation of head direction. Instead, in most of the mismatch sessions, the head direction cell tuning curves rotated as an ensemble clockwise (94%) and in a few sessions rotated counterclockwise (6%). The findings support the notion that the head direction cells may be part of an attractor network bound more strongly to distal landmarks than proximal landmarks, even under conditions in which the CA1 place representation loses its coherence.

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Hippocampal place cells: parallel input streams, subregional processing, and implications for episodic memory.

The hippocampus is thought to be involved in episodic memory in humans. Place cells of the rat hippocampus offer a potentially important model system to understand episodic memory. However, the difficulties in determining whether rats have episodic memory are profound. Progress can be made by considering the hippocampus as a computational device that presumably performs similar transformations on its inputs in both rats and in humans. Understanding the input/output transformations of rat place cells can thus inform research on the computational basis of human episodic memory. Two examples of different transformations in the CA3 and CA1 regions are presented. In one example, CA3 place fields are shown to maintain a greater degree of population coherence than CA1 place fields after a rearrangement of the salient landmarks in an environment, in agreement with computational models of CA3 as an autoassociative network. In the second example, CA3 place field appears to store information about the spatiotemporal sequences of place fields, starting with the first exposure to a cue-altered environment, whereas CA1 place fields store this information only on a temporary basis. Finally, recordings of hippocampal afferents from the lateral and medial entorhinal cortex (EC) suggest that these two regions convey fundamentally different representations to the hippocampus, with spatial information conveyed by the medial EC and nonspatial information conveyed by the lateral EC. The dentate gyrus and CA3 regions may create configural object+place (or item+context) representations that provide the spatiotemporal context of an episodic memory.

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Major dissociation between medial and lateral entorhinal input to dorsal hippocampus.

Hippocampal place cells are a model system of how the brain constructs cognitive representations and of how these representations support complex behavior, learning, and memory. There is, however, a lack of detailed knowledge about the properties of hippocampal afferents. We recorded multiple single units from the hippocampus and the medial and lateral entorhinal areas of behaving rats. Although many medial entorhinal neurons had highly specific place fields, lateral entorhinal neurons displayed weak spatial specificity. This finding demonstrates a fundamental dissociation between the information conveyed to the hippocampus by its major input streams, with spatial information represented by the medial and nonspatial information represented by the lateral entorhinal cortex.

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Ensemble dynamics of hippocampal regions CA3 and CA1.

Computational models based on hippocampal connectivity have proposed that CA3 is uniquely positioned as an autoassociative memory network, capable of performing the competing functions of pattern completion and pattern separation. Recently, three independent studies, two using parallel neurophysiological recording methods and one using immediate-early gene imaging, have examined the responses of CA3 and CA1 ensembles to alterations of environmental context in rats. The results provide converging evidence that CA3 is capable of performing nonlinear transformations of sensory input patterns, whereas CA1 may represent changes in input in a more linear fashion.

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Coupling between place cells and head direction cells during relative translations and rotations of distal landmarks.

Hippocampal place cells are selectively active when a rat occupies restricted locations in an environment, and head direction cells fire selectively when the rat's head is pointed in a particular direction in allocentric space. Both place cells and head direction cells are usually coupled, and they are controlled by a complex interaction between external landmarks and idiothetic cues. Most studies have investigated this interaction by rotating the landmarks in the environment. In contrast, a recent study translated the apparatus relative to the landmarks in an environment and found that most place cells maintained the same preferred location on the apparatus regardless of the location of the apparatus in the room. Because head direction cells are insensitive to the rat's location in an environment, the distal landmarks may influence the place field firing locations primarily by controlling the bearing of the head direction cell system. To address this question, ensembles of CA1 place cells and head direction cells of the anterior thalamus were recorded simultaneously, as a rectangular or circular track was moved to different locations in a room with distinct visual landmarks. Most place cells maintained their firing fields relative to the track when the track was translated, and head direction cells maintained the same preferred firing direction. When the distal landmarks were rotated around the track, the firing fields of place cells and the preferred directions of head direction cells rotated with the cues. These results suggest that the precise firing locations of place cells are controlled by an interaction between local and idiothetic cues, and the orientation of the CA1 ensemble representation relative to the distal landmarks may be controlled indirectly by the distal landmarks' influence over the bearing of the head direction cell system.

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Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3.

The hippocampus, a critical brain structure for navigation, context-dependent learning and episodic memory, is composed of anatomically heterogeneous subregions. These regions differ in their anatomical inputs as well as in their internal circuitry. A major feature of the CA3 region is its recurrent collateral circuitry, by which the CA3 pyramidal cells make excitatory synaptic contacts on each other. In contrast, pyramidal cells in the CA1 region are not extensively interconnected. Although these differences have inspired numerous theoretical models of differential processing capacities of these two regions, there have been few reports of robust differences in the firing properties of CA1 and CA3 neurons in behaving animals. The most extensively studied of these properties is the spatially selective firing of hippocampal 'place cells'. Here we report that in a dynamically changing environment, in which familiar landmarks on the behavioural track and along the wall are rotated relative to each other, the population representation of the environment is more coherent between the original and cue-altered environments in CA3 than in CA1. These results demonstrate a functional heterogeneity between the place cells of CA3 and CA1 at the level of neural population representations.

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A double dissociation between hippocampal subfields: differential time course of CA3 and CA1 place cells for processing changed environments.

Computational theories have suggested different functions for the hippocampal subfields (e.g., CA1 and CA3) in memory. However, it has been difficult to find dissociations relevant to these hypothesized functions in investigations of the hippocampal correlates of space ("place fields") in freely behaving animals. The current study demonstrates a double dissociation between the shifts in the center of mass (COM) of the place fields that were simultaneously recorded in CA1 and CA3 when familiar cue configurations were dynamically changed over days. The COM of CA3 place fields shifted backward in the first experience of the cue-changed environment, whereas the COM of CA1 place fields did not display the backward shift until the next day. These results support the hypothesis that CA3 plays a key role in the rapid formation of representations of new spatiotemporal sequences, whereas CA1 may be more important for comparing currently experienced sequence information with stored sequences in the CA3 network.

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Hippocampus and memory. Can we have our place and fear it too?

Theories of hippocampal function are often split into cognitive map theories and relational/episodic memory theories. In this issue of Neuron, show that hippocampal cells respond to the combination of spatial location and conditioned stimuli in a nonspatial fear conditioning task, suggesting a potential bridge between the competing theories of hippocampal function.

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Distal landmarks and hippocampal place cells: effects of relative translation versus rotation.

Hippocampal neurons are selectively active when a rat occupies restricted locations in an environment. These place cells derive their specificity from a multitude of sources, including idiothetic cues and sensory input derived from both distal and local landmarks. Most experiments have attempted to dissociate the relative strengths and roles played by these sources by rotating one set against the other. Few studies have addressed the effects of relative translation of the local cue set versus salient distal landmarks. To address this question, ensembles of place cells were recorded as a rectangular or circular track was moved to different locations in a room with controlled visual landmarks. Place cells primarily maintained their firing fields relative to the track (i.e., occupying new locations relative to the distal landmarks), even though the track could occupy completely nonoverlapping regions of the room. When the distal landmarks were rotated around the circular track, however, the place fields rotated with the landmarks, demonstrating that the cues were perceptible to the rat. These results suggest that, under these conditions, the spatial tuning of place cells may derive from an interaction between local and idiothetic cues, which define the precise firing locations of the cells and the relationships between them, and distal landmarks, which set the orientation of the ensemble representation relative to the external environment.

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Dynamic interactions between local surface cues, distal landmarks, and intrinsic circuitry in hippocampal place cells.

A number of computational models of hippocampal place cells incorporate attractor neural network architecture to simulate key findings in the place cell literature, including the properties of pattern completion, firing in the absence of visual input, and nonlinear responses to environmental manipulations. To test for evidence of attractor dynamics, ensembles of place cells were recorded using multiple-tetrode techniques. After many days of experience in an environment with salient local surface cues on a circular track and salient distal landmarks on the wall, the local surface cues were rotated as a set in opposition to the distal landmarks. The amount of mismatch between the local and distal sets of cues varied from 45 to 180 degrees. If place cells were parts of strong attractors, then their place fields should follow either the local cues or the distal cues as an integrated ensemble. Instead, in single recording sessions, some place cells were controlled by the distal landmarks, other cells were controlled by the local cues, and other cells became silent or gained new fields. In some cases, individual place fields split in half, following both the local and distal cues. If place cells are indeed parts of attractor networks in the hippocampus, then the attractors may be weak relative to the inputs from external sources, such as representations of the sensory environment and representations of heading direction, in a familiar, well explored environment.

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Neural representations of location outside the hippocampus.

Place cells of the rat hippocampus are a dominant model system for understanding the role of the hippocampus in learning and memory at the level of single-unit and neural ensemble responses. A complete understanding of the information processing and computations performed by the hippocampus requires detailed knowledge about the properties of the representations that are present in hippocampal afferents and efferents in order to decipher the transformations that occur to these representations in the hippocampal circuitry. Neural recordings in behaving rats have revealed a number of brain areas that contain place-related firing properties in the parahippocampal regions and in other brain regions that are thought to interact with the hippocampus in certain behavioral tasks. Although investigators have just begun to scratch the surface in terms of understanding these properties, differences in the precise nature of the spatial firing between the hippocampus and these other regions promise to reveal important clues regarding the exact role of the hippocampus in learning and memory and the nature of its interactions with other brain systems to support adaptive behavior.

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