Oscillatory rhythms in different frequency ranges mark different behavioral states and are thought to provide distinct temporal windows that coherently bind cooperating neuronal assemblies. However, the rhythms in different bands can also interact with each other, suggesting the possibility of higher-order representations of brain states by such rhythmic activity. To explore this possibility, we analyzed local field potential oscillations recorded simultaneously from the striatum and the hippocampus. As rats performed a task requiring active navigation and decision making, the amplitudes of multiple high-frequency oscillations were dynamically modulated in task-dependent patterns by the phase of cooccurring theta-band oscillations both within and across these structures, particularly during decision-making behavioral epochs. Moreover, the modulation patterns uncovered distinctions among both high-and low-frequency subbands. Cross-frequency coupling of multiple neuronal rhythms could be a general mechanism used by the brain to perform networklevel dynamical computations underlying voluntary behavior.amplitude modulation ͉ gamma ͉ theta O scillations in neural population voltage activity are universal phenomena (1). Among brain rhythms, theta oscillations in local field potentials (LFPs) recorded in the hippocampus are prominent during active behaviors (2-5), and these have long been intensively analyzed in the rodent in relation to spatial navigation (6), memory (7), and sleep (8). Theta-band rhythms (4-12 Hz) are now known to occur in other cortical (9-12) and subcortical (12-15) regions, however, including the striatum (14-17), studied here. Gamma oscillations (30-100 Hz) have also received special attention because of their proposed role in functions such as sensory binding (18), selective attention (19-21), transient neuronal assembly formation (22), and information transmission and storage (23-25). The existence of physiologically meaningful neocortical oscillations at even higher frequencies, above the traditional gamma range, has been reported as well (10,(26)(27)(28). In rodents, for example, brief sharp-wave associated ripples (120-200 Hz) appear in the hippocampal formation during slow wave sleep, immobility and consummatory behavior, characteristically in the absence of theta waves (2, 29).The oscillatory activities conventionally assigned to different frequency bands are not completely independent (2-4, 9, 10, 30). In one type of interaction, the phase of low-frequency rhythms modulates the amplitude of higher-frequency oscillations (9, 10, 30). For example, theta phase is known to modulate gamma power in rodent hippocampal and cortical circuits (2-4, 31), and the phase of theta rhythms recorded in the human neocortex can modulate wide-band (60-200 Hz) high-frequency oscillations (10). Such theta-gamma nesting is thought to play a role in sequential memory organization and maintenance of working memory, and more generally in ''phase coding' ' (25, 31). Based on evidence suggesting that theta rhythms i...

Abstract. We have defined a signal responsible for the morphological differentiation of human umbilical vein and human dermal microvascular endothelial cells in vitro. We find that human umbilical vein endothelial cells deprived of growth factors undergo morphological differentiation with tube formation after 6-12 wk, and that human dermal microvascular endothelial cells differentiate after 1 wk of growth factor deprivation. Here, we report that morphological differentiation of both types of endothelial cells is markedly accelerated by culture on a reconstituted gel composed of basement membrane proteins. Under these conditions, tube formation begins in 1-2 h and is complete by 24 h. The tubes are maintained for >2 wk. Little or no proliferation occurs under these conditions, although the cells, when trypsinized and replated on fibronectin-coated tissue culture dishes, resume division. U1-trastructurally, the tubes possess a lumen surrounded by endothelial cells attached to one another by junctional complexes. The cells possess Weibel-Palade bodies and factor VIII-related antigens, and take up acetylated low density lipoproteins. Tubule formation does not occur on tissue culture plastic coated with laminin or collagen IV, either alone or in combination, or on an agarose or a collagen I gel. However, endothelial cells cultured on a collagen I gel supplemented with laminin form tubules, while supplementation with collagen IV induces a lesser degree of tubule formation. Preincubation of endothelial cells with antibodies to laminin prevented tubule formation while antibodies to collagen IV were less inhibitory. Preincubation of endotheial cells with synthetic peptides derived from the laminin B1 chain that bind to the laminin cell surface receptor or incorporation of these peptides into the gel matrix blocked tubule formation, whereas control peptides did not. These observations indicate that endothelial cells can rapidly differentiate on a basement membrane-like matrix and that laminin is the principal factor in inducing this change.

Learning to perform a behavioural procedure as a well-ingrained habit requires extensive repetition of the behavioural sequence, and learning not to perform such behaviours is notoriously difficult. Yet regaining a habit can occur quickly, with even one or a few exposures to cues previously triggering the behaviour. To identify neural mechanisms that might underlie such learning dynamics, we made long-term recordings from multiple neurons in the sensorimotor striatum, a basal ganglia structure implicated in habit formation, in rats successively trained on a reward-based procedural task, given extinction training and then given reacquisition training. The spike activity of striatal output neurons, nodal points in cortico-basal ganglia circuits, changed markedly across multiple dimensions during each of these phases of learning. First, new patterns of task-related ensemble firing successively formed, reversed and then re-emerged. Second, task-irrelevant firing was suppressed, then rebounded, and then was suppressed again. These changing spike activity patterns were highly correlated with changes in behavioural performance. We propose that these changes in task representation in cortico-basal ganglia circuits represent neural equivalents of the explore-exploit behaviour characteristic of habit learning.