Hippocampal granule cells opt for early retirement.

Increased excitability and plasticity of adult-generated hippocampal granule cells during a critical period suggests that they may "orthogonalize" memories according to time. One version of this "temporal tag" hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90-95%, are effectively "retired." If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard "orthogonalizer" theory of the role of the dentate gyrus in memory.

Context-specific spatial representations by lateral septal cells.

To test whether the location coding of lateral septal cells is dependent on cue constellations, we examined single units in two different recording arenas on alternating days. Repeated recordings of lateral septal neurons in the same arena revealed that matching locations are encoded on separate days by about one third of the cells. The cells typically showed location-selective firing in only one of the two recording arenas and initially showed unrelated patterns when tested in a different recording arena. When tested for a second time in each recording arena, the initially dissimilar patterns were modified towards increased similarity between arenas. Simultaneously recorded hippocampal principal cells showed distinct place fields for each recording arena throughout the recording sequence. These results indicate that the initial reorganization of the lateral septal location coding may occur as a direct consequence of the hippocampal reorganization. Further septal reorganization is then partially independent of established place fields in the CA1 and CA3 area.Location-selective cells in cortical areas that receive projections from hippocampus proper (i.e. the subiculum and the entorhinal cortex) have not been shown to encode differences between recording arenas. Although some characteristics of this generalized coding scheme have also been found for location-selective lateral septal cells, the encoding of context information was generally preserved in the subcortical target cells of projections from the CA1 and CA3 area.

Dorsal striatal head direction and hippocampal place representations during spatial navigation.

Several theories of basal ganglia function describe a striatal contribution to learning that is independent of hippocampal function. This study examined the question of whether the striatum should be regarded as functioning independently of or acting in concert with limbic structures. Dorsal striatal head direction cells and hippocampal place cells were recorded in parallel while rats performed a hippocampal-dependent radial maze task. Changes in the directional preference of head direction cells and the location of place fields were compared following alterations of the sensory environment. When familiar visual cues were presented in new spatial arrangements, or when new visual cues were placed in a familiar environment, rotations of directional preferences were consistent with the mean place-field response. When familiar visual and nonvisual cues were presented in conflict, or when rats were exposed to novel environments, the responses of the two cell types were inconsistent relative to each other. This pattern suggests that current perceptions and expectations of familiar spatial contexts may dynamically modulate the relationship between hippocampus and dorsal striatum.

Directing place representation in the hippocampus.

Theoretical models of rodent navigation consider location information and directional heading to be essential. Indeed, the existence of location-selective 'place cells' and orientation-selective 'head direction cells' is well documented. Different models suggest different forms of interaction between information about location and heading direction. However, until recently, there were no clear empirical data that could be used to distinguish the different models in terms of the nature of the integration of location and directional heading information. Recently, Leutgeb et al. provided evidence that head direction and place signals coexist within the CA1 region of hippocampus, and that the head direction signals are likely to be generated by a subpopulation of interneurons. This finding opens up new possibilities for clarifying current models and for developing biologically plausible theories of synaptic interactions between location and head direction codes. In this paper, we first present the issue concerning the nature of the interaction between location and head direction signals, followed by a selective review of place and head direction cell research. The finding of Leutgeb et al. is then summarized, and its implications for current models are discussed. Finally, a view is presented that considers place fields to be a product not only of (external and internal) sensory input, but also of non-spatial variables such as motivation and responses. The finding of Leutgeb et al. and many earlier anatomical studies suggest that hippocampal head direction, motivation and response information may be represented by the interneuron population. Thus, these factors may have strong impact on the location codes of hippocampal pyramidal neurons. Their influence may further define the behavioral context of the current spatial environment.

Convergence of head direction and place information in the CA1 region of hippocampus.

The hippocampus has long been considered critical for spatial learning and navigation. Recent theoretical models of the rodent and primate hippocampus consider spatial processing a special case of a more general memory function. These non-spatial theories of hippocampus differ from navigational theories with respect to the role of self-motion representations. The present study presents evidence for a new cell type in the CA1 area of the rat hippocampus that codes for directional heading independent of location information (i.e. the angular component of self-motion). These hippocampal head direction cells are controlled by external and idiothetic cues in a similar way as head direction cells in other brain areas and hippocampal place cells. Convergent head direction information and location information may be an essential component of a neural system that monitors behavioral sequences during navigation. Conflicts between internally generated and external cues have previously been shown to result in new hippocampal place representations, suggesting that head direction information may participate in synaptic interactions when new location codes are formed. Combined hippocampal representations of self-motion and external cues may therefore contribute to path integration as well as spatial memory processing.

A neural systems analysis of adaptive navigation.

In the field of the neurobiology of learning, significant emphasis has been placed on understanding neural plasticity within a single structure (or synapse type) as it relates to a particular type of learning mediated by a particular brain area. To appreciate fully the breadth of the plasticity responsible for complex learning phenomena, it is imperative that we also examine the neural mechanisms of the behavioral instantiation of learned information, how motivational systems interact, and how past memories affect the learning process. To address this issue, we describe a model of complex learning (rodent adaptive navigation) that could be used to study dynamically interactive neural systems. Adaptive navigation depends on the efficient integration of external and internal sensory information with motivational systems to arrive at the most effective cognitive and/or behavioral strategies. We present evidence consistent with the view that during navigation: 1) the limbic thalamus and limbic cortex is primarily responsible for the integration of current and expected sensory information, 2) the hippocampal-septal-hypothalamic system provides a mechanism whereby motivational perspectives bias sensory processing, and 3) the amygdala-prefrontal-striatal circuit allows animals to evaluate the expected reinforcement consequences of context-dependent behavioral responses. Although much remains to be determined regarding the nature of the interactions among neural systems, new insights have emerged regarding the mechanisms that underlie flexible and adaptive behavioral responses.

Hippocampal representational organization and spatial context.

The hippocampus appears to undergo continual representational reorganization as animals navigate their environments. This reorganization is postulated to be reflected spatially in terms of changes in the ensemble of place cells activated, as well as changes in place field specificity and reliability for cells recorded in both hilar/CA3 and CA1 regions. The specific contribution of the hilar/CA3 region is suggested to be to compare the expected spatial context with that currently being experienced, then relay discrepancies to CA1. The properties of CA1 place fields in part reflect the spatial comparisons made in the hilar/CA3 area. In addition, CA1 organizes the input received from the hilar/CA3 place cells according to different temporal algorithms that are unique to different tasks. In this way, hippocampus helps to distinguish temporally one spatial context from another, thereby contributing to episodic memories.

Excitotoxic septal lesions result in spatial memory deficits and altered flexibility of hippocampal single-unit representations.

The septal nuclei are reciprocally connected with the hippocampal formation and contribute importantly to spatial and memory processing. Using excitotoxic lesions of the septal area, we investigated whether neurodegeneration in subcortical projections to hippocampus can compromise flexible information processing by hippocampal single units. In agreement with the mild effects of excitotoxic septal lesions on hippocampal physiology compared with fimbria-fornix lesions and septal inactivation, we observed limited lesion effects on single-unit activity. The location specificity of hippocampal complex spike cells remained unchanged, but a less reliable location-dependent discharge was observed in experimental animals with a pronounced postoperative working memory deficit. Testing in the absence of ambient illumination and in a new environment revealed that the spatial correlates of complex spike cells in lesioned animals may rely on a more limited set of sensory cues. Altered sensory cues resulted in a significantly different response pattern between the control and lesion group in the new environment, a situation that normally results in place field reorganization. Such a group difference was not observed during dark testing, a condition in which place field reorganization is less prominent. A contribution of hippocampal interneurons to the observed alterations in the spatial properties of the principal cells was suggested by decreased theta modulation in the lesioned group. Because excitotoxic lesions result in memory deficits that resemble age-related memory problems in the absence of age-related degenerative processes, we suggest that septal neurodegeneration could directly contribute to those behavioral changes with advanced age that correlate with functional alterations in the hippocampal formation.

Signal timing across the macaque visual system.

The onset latencies of single-unit responses evoked by flashing visual stimuli were measured in the parvocellular (P) and magnocellular (M) layers of the dorsal lateral geniculate nucleus (LGNd) and in cortical visual areas V1, V2, V3, V4, middle temporal area (MT), medial superior temporal area (MST), and in the frontal eye field (FEF) in individual anesthetized monkeys. Identical procedures were carried out to assess latencies in each area, often in the same monkey, thereby permitting direct comparisons of timing across areas. This study presents the visual flash-evoked latencies for cells in areas where such data are common (V1 and V2), and are therefore a good standard, and also in areas where such data are sparse (LGNd M and P layers, MT, V4) or entirely lacking (V3, MST, and FEF in anesthetized preparation). Visual-evoked onset latencies were, on average, 17 ms shorter in the LGNd M layers than in the LGNd P layers. Visual responses occurred in V1 before any other cortical area. The next wave of activation occurred concurrently in areas V3, MT, MST, and FEF. Visual response latencies in areas V2 and V4 were progressively later and more broadly distributed. These differences in the time course of activation across the dorsal and ventral streams provide important temporal constraints on theories of visual processing.

Telencephalic afferents to the caudolateral neostriatum of the pigeon.

The pigeon caudolateral neostriatum (NCL) shares a dopaminergic innervation with mammalian frontal cortical areas and is implicated in the regulation of avian cognitive behavior. Retrograde tracing methods were used to identify forebrain projections to NCL and to suggest a possible role of this area in mediating spatial behavior. NCL receives telencephalic projections from the hyperstriatum accessorium, cells along the border of hyperstriatum dorsale and hyperstriatum ventrale, anterolateral hyperstriatum adjacent to the vallecula, confined cell groups within the anterior neostriatum, and subdivisions of the archistriatum. In addition, labeling of a small number of large cells near the fasciculus prosencephali lateralis was observed at the level of the anterior commissure. In accordance with previous studies, projections of subtelencephalic areas were revealed to originate from the thalamic posterior dorsolateral nucleus and nucleus subrotundus, as well as from the tegmental nucleus pedunculopontinus and locus coeruleus. Forebrain connections of NCL show that somatosensory, visual, and olfactory information can combine in this division of the neostriatum. NCL is therefore suited to participate in a neural circuit that regulates spatial behavior. Moreover, the present study reveals that NCL is reached by a limbic projection from the nucleus taeniae. This projection also suggests similarity between NCL and mammalian frontal cortical areas.