Distributed cell assemblies spanning prefrontal cortex and striatum.

Highly synchronous neuronal assembly activity is deemed essential for cognitive brain function. In theory, such synchrony could coordinate multiple brain areas performing complementary processes. However, cell assemblies have been observed only in single structures, typically cortical areas, and little is known about their synchrony with downstream subcortical structures, such as the striatum. Here, we demonstrate distributed cell assemblies activated at high synchrony (∼10 ms) spanning prefrontal cortex and striatum. In addition to including neurons at different brain hierarchical levels, surprisingly, they synchronized functionally distinct limbic and associative sub-regions. These assembly activations occurred when members shifted their firing phase relative to ongoing 4 Hz and theta rhythms, in association with high gamma oscillations. This suggests that these rhythms could mediate the emergence of cross-structural assemblies. To test for the role of assemblies in behavior, we trained the rats to perform a task requiring cognitive flexibility, alternating between two different rules in a T-maze. Overall, assembly activations were correlated with task-relevant parameters, including impending choice, reward, rule, or rule order. Moreover, these behavioral correlates were more robustly expressed by assemblies than by their individual member neurons. Finally, to verify whether assemblies can be endogenously generated, we found that they were indeed spontaneously reactivated during sleep and quiet immobility. Thus, cell assemblies are a more general coding mechanism than previously envisioned, linking distributed neocortical and subcortical areas at high synchrony.

Retrospectively and prospectively modulated hippocampal place responses are differentially distributed along a common path in a continuous T-maze.

Hippocampal place responses can be prospectively or retrospectively modulated by the animal's future or prior trajectory. Two main hypotheses explain this. The "multiple-map hypothesis" switches between different maps for different trajectories (rate remapping). In contrast, in the "buffer hypothesis," the hippocampus encodes an ongoing representation that includes the recent past and/or the impending future choice. This study examines the distribution of prospective and retrospective responses distributed along a common path in a continuous T-maze (providing all four combinations of provenance and destination) during a visual discrimination task. The multiple-map hypothesis predicts either uniform distributions or concerted shifts about a task-decision relevant point, whereas the buffer hypothesis predicts a time-limited overexpression around choice points (with retrospective responses after the central arm entry point and prospective responses nearer its exit). Here bilateral recordings in the dorsal CA1 region of the rat hippocampus show that retrospective responses were twice as prevalent as prospective responses. Furthermore, retrospective and prospective modulations have distinct spatial distributions, with retrospective primarily in the first two-thirds of the central arm and prospective restricted to the last third. To test for possible trial-by-trial remapping in relation to the two-thirds transition point, data from the first and second halves of the sessions were compared. Backward drift of path-modulated activity was significant only for retrospective, but not prospective, fields. Thus, these data are more consistent with the buffer hypothesis. Retrospective and prospective modulation would then participate in a single hippocampal representation of spatial and behavioral context.

Optic flow stimuli update anterodorsal thalamus head direction neuronal activity in rats.

Head direction (HD) neurons fire selectively according to head orientation in the yaw plane relative to environmental landmark cues. Head movements provoke optic field flow signals that enter the vestibular nuclei, indicating head velocity, and hence angular displacements. To test whether optic field flow alone affects the directional firing of HD neurons, rats walked about on a circular platform as a spot array was projected onto the surrounding floor-to-ceiling cylindrical black curtain. Directional responses in the anterodorsal thalamus of four rats remained stable as they moved about with the point field but in the absence of landmark cues. Then, the spherical projector was rotated about its yaw axis at 4.5°/s for ∼90 s. In 27 sessions the mean drift speed of the preferred directions (PDs) was 1.48°/s (SD=0.78°/s; range: 0.15 to 2.88°/s). Thus, optic flow stimulation entrained PDs, albeit at drift speeds slower than the field rotation. This could be due to conflicts with vestibular, motor command, and efferent copy signals. After field rotation ended, 20/27 PDs drifted back to within 45° of the initial values over several minutes, generally following the shortest path to return to the initial value. Poststimulation drifts could change speed and/or direction, with mean speeds of 0.68±0.64°/s (range 0 to 1.36°/s). Since the HD cell pathway (containing anterodorsal thalamus) is the only known projection of head direction information to entorhinal grid cells and hippocampal place cells, yaw plane optic flow signals likely influence representations in this spatial reference coordinate system for orientation and navigation.

Selective suppression of hippocampal ripples impairs spatial memory.

Sharp wave-ripple (SPW-R) complexes in the hippocampus-entorhinal cortex are believed to be important for transferring labile memories from the hippocampus to the neocortex for long-term storage. We found that selective elimination of SPW-Rs during post-training consolidation periods resulted in performance impairment in rats trained on a hippocampus-dependent spatial memory task. Our results provide evidence for a prominent role of hippocampal SPW-Rs in memory consolidation.

Passive movements of the head do not abolish anticipatory firing properties of head direction cells.

Neurons in the anterior dorsal thalamic nucleus (ADN) of the rat selectively discharge in relation to the animal's head direction (HD) in the horizontal plane. Temporal analyses of cell firing properties reveal that their discharge is optimally correlated with the animal's future directional heading by approximately 24 ms. Among the hypotheses proposed to explain this property is that ADN HD cells are informed of future head movement via motor efference copy signals. One prediction of this hypothesis is that when the rat's head is moved passively, the anticipatory time interval (ATI) will be attenuated because the motor efference signal reflects only the active contribution to the movement. The present study tested this hypothesis by loosely restraining the animal and passively rotating it through the cell's preferred direction. Contrary to our prediction, we found that ATI values did not decrease during passive movement but in fact increased significantly. HD cells in the postsubiculum did not show the same effect, suggesting independence between the two sites with respect to anticipatory firing. We conclude that it is unlikely that a motor efference copy signal alone is responsible for generating anticipatory firing in ADN HD cells.

Spike phase precession persists after transient intrahippocampal perturbation.

Oscillatory spike timing in the hippocampus is regarded as a temporal coding mechanism for space, but the underlying mechanisms are poorly understood. To contrast the predictions of the different models of phase precession, we transiently turned off neuronal discharges for up to 250 ms and reset the phase of theta oscillations by stimulating the commissural pathway in rats. After recovery from silence, phase precession continued. The phase of spikes for the first theta cycle after the perturbation was more advanced than the phase of spikes for the last theta cycle just before the perturbation. These findings indicate that phase advancement that emerges within hippocampal circuitry may be updated at the beginning of each theta cycle by extrahippocampal inputs.

Rat anterodorsal thalamic head direction neurons depend upon dynamic visual signals to select anchoring landmark cues.

Head direction cells, which are functionally coupled to 'place' cells of the hippocampus, a structure critically involved in spatial cognition, are likely neural substrates for the sense of direction. Here we studied the mechanism by which head direction cells are principally anchored to background visual cues [M.B. Zugaro et al. (2001) J. Neurosci., 21, RC154,1-5]. Anterodorsal thalamic head direction cells were recorded while the rat foraged on a small elevated platform in a 3-m diameter cylindrical enclosure. A large card was placed in the background, near the curtain, and a smaller card was placed in the foreground, near the platform. The cards were identically marked, proportionally dimensioned, subtended the same visual angles from the central vantage point and separated by 90 degrees. The rat was then disoriented in darkness, the cards were rotated by 90 degrees in opposite directions about the center and the rat was returned. Preferred directions followed either the background card, foreground card or midpoint between the two cards. In continuous lighting, preferred directions shifted to follow the background cue in most cases (30 of the 53 experiments, Batschelet V-test, P < 0.01). Stroboscopic illumination, which perturbs dynamic visual signals (e.g. motion parallax), blocked this selectivity. Head direction cells remained equally anchored to the background card, foreground card or configuration of the two cards (Watson test, P > 0.1). This shows that dynamic visual signals are critical in distinguishing typically more stable background cues which govern spatial neuronal responses and orientation behaviors.

Rapid spatial reorientation and head direction cells.

It is surprising how quickly we can find our bearings when suddenly confronted with a familiar environment, for instance when the lights are turned on in a dark room. Subjectively, this appears to occur almost instantaneously, yet the neural processes permitting this rapid reorientation are unknown. A likely candidate is the head direction (HD) cell system. These limbic neurons found in several brain regions, including the thalamus and the hippocampus, discharge selectively when the head of an animal is oriented in a particular ("preferred") direction. This neuronal activity is independent of position and ongoing behavior and is thus likely to constitute a physiological basis for the sense of direction. Remarkably, although the HD cell system has properties resembling those of a compass, it is independent of geomagnetic fields. Rather, the preferred directions of the HD cells are strongly anchored to visual cues in the environment. Here, we bring evidence for the first time that a fundamental component of the capacity to rapidly reorient in a familiar environment may be brought about by updating of HD cell responses as rapidly as 80 msec after changes in the visual scene. Continuous attractor networks have been used successfully to model HD cell ensemble dynamics. The present results suggest that after large rotations of the surrounding landmarks, activity in such networks may be propagated in abrupt jumps rather than in a gradually progressive manner.

Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations.

Head direction cells discharge selectively when the head of the animal is oriented in a specific direction. The goal of this study was to determine how sensory signals arising from passive rotations (e.g., triggered by vestibular stimulation and dynamic visual inputs) influence the responses of anterodorsal thalamic head direction cells in the absence of voluntary movement cues (e.g., motor command, efference copy, and associated kinesthetic signals). Three unrestrained rats consumed water from a reservoir at the center of a circular platform while passively subjected to sinusoidal rotatory oscillations at fast (153 +/- 27 degrees/s, sd) and slow (38 +/- 15 degrees/s) peak velocities. In 14 anterodorsal thalamic head direction cells, the preferred directions, angular response ranges and baseline firing rates remained stable, but the peak firing rates were, on average, 36% higher during the fast rotations (Wilcoxon matched-pairs test, p < 0.001; variation range: +11% to approximately +100%). No cell changed its peak firing rate by less than 10%, while three cells (21%) increased their peak firing rates by more than 50%. The velocity-dependent increase in peak firing rates was similar for left and right rotations, and the skewness of the directional response curves were not significantly different between left and right turns (Wilcoxon matched-pairs tests, n = 14, ns). These results show that sensory signals concerning self-movements modulate the responses of the head direction cells in the absence of active locomotion.

Multisensory processing in the elaboration of place and head direction responses by limbic system neurons.

This review explores the roles of several sensory modalities in the establishment and maintenance of discharges correlated with head position and orientation in neurons of the hippocampus and associated structures in the Papez circuit. Focus is placed on the integration of signals related to environmental cues and to displacement movements, both of external and internal origin. While the visual, vestibular and motor systems each exert influences, position and head direction signals are nevertheless maintained in the absence of any one of these respective inputs. Context-related changes in hippocampal discharge correlates are also highlighted. These characteristics provide these signals with robustness and flexibility, properties particularly suited for cognitive processes such as contextual processing, memory and planning.