Anton Sirota

Entrainment of Neocortical Neurons and Gamma Oscillations by the Hippocampal Theta Rhythm

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.

Communication between neocortex and hippocampus during sleep in rodents

Both neocortical and hippocampal networks organize the firing patterns of their neurons by prominent oscillations during sleep, but the functional role of these rhythms is not well understood. Here, we show a robust correlation of neuronal discharges between the somatosensory cortex and hippocampus on both slow and fine time scales in the mouse and rat. Neuronal bursts in deep cortical layers, associated with sleep spindles and delta waves/slow rhythm, effectively triggered hippocampal discharges related to fast (ripple) oscillations. We hypothesize that oscillation-mediated temporal links coordinate specific information transfer between neocortical and hippocampal cell assemblies. Such a neocortical–hippocampal interplay may be important for memory consolidation.

Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop.

Theta oscillations are believed to play an important role in the coordination of neuronal firing in the entorhinal (EC)-hippocampal system but the underlying mechanisms are not known. We simultaneously recorded from neurons in multiple regions of the EC-hippocampal loop and examined their temporal relationships. Theta-coordinated synchronous spiking of EC neuronal populations predicted the timing of current sinks in target layers in the hippocampus. However, the temporal delays between population activities in successive anatomical stages were longer (typically by a half theta cycle) than expected from axon conduction velocities and passive synaptic integration of feed-forward excitatory inputs. We hypothesize that the temporal windows set by the theta cycles allow for local circuit interactions and thus a considerable degree of computational independence in subdivisions of the EC-hippocampal loop.

Early motor activity drives spindle bursts in the developing somatosensory cortex

Sensorimotor coordination emerges early in development. The maturation period is characterized by the establishment of somatotopic cortical maps, the emergence of long-range cortical connections, heightened experience-dependent plasticity and spontaneous uncoordinated skeletal movement. How these various processes cooperate to allow the somatosensory system to form a three-dimensional representation of the body is not known. In the visual system, interactions between spontaneous network patterns and afferent activity have been suggested to be vital for normal development. Although several intrinsic cortical patterns of correlated neuronal activity have been described in developing somatosensory cortex in vitro, the in vivo patterns in the critical developmental period and the influence of physiological sensory inputs on these patterns remain unknown. We report here that in the intact somatosensory cortex of the newborn rat in vivo, spatially confined spindle bursts represent the first and only organized network pattern. The localized spindles are selectively triggered in a somatotopic manner by spontaneous muscle twitches, motor patterns analogous to human fetal movements. We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination.

Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats

Low intensity electric fields have been suggested to affect the ongoing neuronal activity in vitro and in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performed in vivo extracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity.

Theta and Gamma Coordination of Hippocampal Networks during Waking and Rapid Eye Movement Sleep

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 (∼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.

Distinct Representations and Theta Dynamics in Dorsal and Ventral Hippocampus

Although anatomical, lesion, and imaging studies of the hippocampus indicate qualitatively different information processing along its septo-temporal axis, physiological mechanisms supporting such distinction are missing. We found fundamental differences between the dorsal (dCA3) and the ventral-most parts (vCA3) of the hippocampus in both environmental representation and temporal dynamics. Discrete place fields of dCA3 neurons evenly covered all parts of the testing environments. In contrast, vCA3 neurons (1) rarely showed continuous two-dimensional place fields, (2) differentiated open and closed arms of a radial maze, and (3) discharged similar firing patterns with respect to the goals, both on multiple arms of a radial maze and during opposite journeys in a zigzag maze. In addition, theta power and the fraction of theta-rhythmic neurons were substantially reduced in the ventral compared with dorsal hippocampus. We hypothesize that the spatial representation in the septo-temporal axis of the hippocampus is progressively decreased. This change is paralleled with a reduction of theta rhythm and an increased representation of nonspatial information.

Band-tunable and multiplexed integrated circuits for simultaneous recording and stimulation with microelectrode arrays

Two thin-film microelectrode arrays with integrated circuitry have been developed for extracellular neural recording in behaving animals. An eight-site probe for simultaneous neural recording and stimulation has been designed that includes on-chip amplifiers that can be individually bypassed, allowing direct access to the iridium sites for electrical stimulation. The on-probe amplifiers have a gain of 38.9 dB, an upper-cutoff frequency of 9.9 kHz, and an input-referred noise of 9.2 /spl mu/V /sub rms/ integrated from 100 Hz to 10 kHz. The low-frequency cutoff of the amplifier is tunable to allow the recording of field potentials and minimize stimulus artifact. The amplifier consumes 68 /spl mu/W from /spl plusmn/1.5 V supplies and occupies 0.177 mm/sup 2/ in 3 /spl mu/m features. In vivo recordings have shown that the preamplifiers can record single-unit activity 1 ms after the onset of stimulation on sites as close as 20 /spl mu/m to the stimulating electrode. A second neural recording array has been developed which multiplexes 32 neural signals onto four output data leads. Providing gain on this array eliminates the need for bulky head-mounted circuitry and reduces motion artifacts. The time-division multiplexing circuitry has crosstalk between consecutive channels of less than 6% at a sample rate of 20 kHz per channel. Amplified, time-division-multiplexed multichannel neural recording allows the large-scale recording of neuronal activity in freely behaving small animals with minimum number of interconnect leads.

Hippocampal place cell assemblies are speed-controlled oscillators

The phase of spikes of hippocampal pyramidal cells relative to the local field θ oscillation shifts forward (“phase precession”) over a full θ cycle as the animal crosses the cells receptive field (“place field”). The linear relationship between the phase of the spikes and the travel distance within the place field is independent of the animals running speed. This invariance of the phase–distance relationship is likely to be important for coordinated activity of hippocampal cells and space coding, yet the mechanism responsible for it is not known. Here we show that at faster running speeds place cells are active for fewer θ cycles but oscillate at a higher frequency and emit more spikes per cycle. As a result, the phase shift of spikes from cycle to cycle (i.e., temporal precession slope) is faster, yet spatial-phase precession stays unchanged. Interneurons can also show transient-phase precession and contribute to the formation of coherently precessing assemblies. We hypothesize that the speed-correlated acceleration of place cell assembly oscillation is responsible for the phase–distance invariance of hippocampal place cells.

Interaction between neocortical and hippocampal networks via slow oscillations

Both the thalamocortical and limbic systems generate a variety of brain state-dependent rhythms but the relationship between the oscillatory families is not well understood. Transfer of information across structures can be controlled by the offset oscillations. We suggest that slow oscillation of the neocortex, which was discovered by Mircea Steriade, temporally coordinates the self-organized oscillations in the neocortex, entorhinal cortex, subiculum and hippocampus. Transient coupling between rhythms can guide bidirectional information transfer among these structures and might serve to consolidate memory traces.