Faculty Bibliography

Rapid eye movement (REM) sleep has been considered a paradoxical state because, despite the high behavioral threshold to arousing perturbations, gross physiological patterns in the forebrain resemble those of waking states. To understand how intrahippocampal networks interact during REM sleep, we used 96 site silicon probes to record from different hippocampal subregions and compared the patterns of activity during waking exploration and REM sleep. Dentate/CA3 theta and gamma synchrony was significantly higher during REM sleep compared with active waking. In contrast, gamma power in CA1 and CA3-CA1 gamma coherence showed significant decreases in REM sleep. Changes in unit firing rhythmicity and unit-field coherence specified the local generation of these patterns. Although these patterns of hippocampal network coordination characterized the more common tonic periods of REM sleep (approximately 95% of total REM), we also detected large phasic bursts of local field potential power in the dentate molecular layer that were accompanied by transient increases in the firing of dentate and CA1 neurons. In contrast to tonic REM periods, phasic REM epochs were characterized by higher theta and gamma synchrony among the dentate, CA3, and CA1 regions. These data suggest enhanced dentate processing, but limited CA3-CA1 coordination during tonic REM sleep. In contrast, phasic bursts of activity during REM sleep may provide windows of opportunity to synchronize the hippocampal trisynaptic loop and increase output to cortical targets. We hypothesize that tonic REM sleep may support off-line mnemonic processing, whereas phasic bursts of activity during REM may promote memory consolidation

Although short-term plasticity is believed to play a fundamental role in cortical computation, empirical evidence bearing on its role during behavior is scarce. Here we looked for the signature of short-term plasticity in the fine-timescale spiking relationships of a simultaneously recorded population of physiologically identified pyramidal cells and interneurons, in the medial prefrontal cortex of the rat, in a working memory task. On broader timescales, sequentially organized and transiently active neurons reliably differentiated between different trajectories of the rat in the maze. On finer timescales, putative monosynaptic interactions reflected short-term plasticity in their dynamic and predictable modulation across various aspects of the task, beyond a statistical accounting for the effect of the neurons' co-varying firing rates. Seeking potential mechanisms for such effects, we found evidence for both firing pattern-dependent facilitation and depression, as well as for a supralinear effect of presynaptic coincidence on the firing of postsynaptic targets

Brain oscillations are important in controlling the timing of neuronal firing. This process has been extensively analyzed in connection with gamma frequency oscillations and more recently with respect to theta frequency oscillations. Here we review evidence that theta and gamma oscillations work together to form a neural code. This coding scheme provides a way for multiple neural ensembles to represent an ordered sequence of items. In the hippocampus, this coding scheme is utilized during the phase precession, a phenomenon that can be interpreted as the recall of sequences of items (places) from long-term memory. The same coding scheme may be used in certain cortical regions to encode multi-item short-term memory. The possibility that abnormalities in theta/gamma could underlie symptoms of schizophrenia is discussed

A long-standing conjecture in neuroscience is that aspects of cognition depend on the brain's ability to self-generate sequential neuronal activity. We found that reliably and continually changing cell assemblies in the rat hippocampus appeared not only during spatial navigation but also in the absence of changing environmental or body-derived inputs. During the delay period of a memory task, each moment in time was characterized by the activity of a particular assembly of neurons. Identical initial conditions triggered a similar assembly sequence, whereas different conditions gave rise to different sequences, thereby predicting behavioral choices, including errors. Such sequences were not formed in control (nonmemory) tasks. We hypothesize that neuronal representations, evolved for encoding distance in spatial navigation, also support episodic recall and the planning of action sequences

Although it has been tacitly assumed that the hippocampus exerts an influence on neocortical networks, the mechanisms of this process are not well understood. We examined whether and how hippocampal theta oscillations affect neocortical assembly patterns by recording populations of single cells and transient gamma oscillations in multiple cortical regions, including the somatosensory area and prefrontal cortex in behaving rats and mice. Laminar analysis of neocortical gamma bursts revealed multiple gamma oscillators of varying frequency and location, which were spatially confined and synchronized local groups of neurons. A significant fraction of putative pyramidal cells and interneurons as well as localized gamma oscillations in all recorded neocortical areas were phase biased by the hippocampal theta rhythm. We hypothesize that temporal coordination of neocortical gamma oscillators by hippocampal theta is a mechanism by which information contained in spatially widespread neocortical assemblies can be synchronously transferred to the associative networks of the hippocampus

The hippocampus provides a spatial map of the environment. Changes in the environment alter the firing patterns of hippocampal neurons, but are presumably constrained by elements of the network dynamics. We compared the neural activity in CA1 and CA3 regions of the hippocampus in rats running for water reward on a linear track, before and after the track length was shortened. A fraction of cells lost their place fields and new sets of cells with fields emerged, indicating distinct representation of the two tracks. Cells active in both environments shifted their place fields in a location-dependent manner, most notably at the beginning and the end of the track. Furthermore, peak firing rates and place-field sizes decreased, whereas place-field overlap and coactivity increased. Power in the theta-frequency band of the local field potentials also decreased in both CA1 and CA3, along with the coherence between the two structures. In contrast, the theta-scale (0-150 ms) time lags between cell pairs, representing distances on the tracks, were conserved, and the activity of the inhibitory neuron population was maintained across environments. We interpret these observations as reflecting the freedoms and constraints of the hippocampal network dynamics. The freedoms permit the necessary flexibility for the network to distinctly represent unique patterns, whereas the dynamics constrain the speed at which activity propagates between the cell assemblies representing the patterns

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization

The zona incerta (ZI) is at the crossroad of almost all major ascending and descending fiber tracts and targets numerous brain centers from the thalamus to the spinal cord. Effective ascending drive of ZI cells has been described, but the role of descending cortical signals in patterning ZI activity is unknown. Cortical control over ZI function was examined during slow cortical waves (1-3 Hz), paroxysmal high-voltage spindles (HVSs), and 5-9 Hz oscillations in anesthetized rats. In all conditions, rhythmic cortical activity significantly altered the firing pattern of ZI neurons recorded extracellularly and labeled with the juxtacellular method. During slow oscillations, the majority of ZI neurons became synchronized to the depth-negative phase ('up state') of the cortical waves to a degree comparable to thalamocortical neurons. During HVSs, ZI cells displayed highly rhythmic activity in tight synchrony with the cortical oscillations. ZI neurons responded to short epochs of cortical 5-9 Hz oscillations, with a change in the interspike interval distribution and with an increase in spectral density in the 5-9 Hz band as measured by wavelet analysis. Morphological reconstruction revealed that most ZI cells have mediolaterally extensive dendritic trees and very long dendritic segments. Cortical terminals established asymmetrical synapses on ZI cells with very long active zones. These data suggest efficient integration of widespread cortical signals by single ZI neurons and strong cortical drive. We propose that the efferent GABAergic signal of ZI neurons patterned by the cortical activity can play a critical role in synchronizing thalamocortical and brainstem rhythms