Place-modulated activity among neurons in the hippocampal formation presents a means to organize contextual information in the service of memory formation and recall1,2. One particular spatial representation, that of grid cells, has been observed in the entorhinal cortex (EC) of rats and bats3–5, but has yet to be described in single units in primates. Here, we examined spatial representations in the EC of head-fixed monkeys performing a free-viewing visual memory task6,7. Individual neurons were identified in the primate EC that emitted action potentials when the monkey fixated multiple discrete locations in the visual field across the presentation of up to hundreds of novel images. These firing fields possess spatial periodicity similar to a triangular tiling with a corresponding well-defined hexagonal structure in the spatial autocorrelation. Further, these neurons demonstrated theta-band oscillatory activity and changing spatial scale as a function of distance from the rhinal sulcus, which is consistent with previous findings in rodents4,8–10. These spatial representations may provide a framework to anchor the encoding of stimulus content in a complex visual scene. Together, our results provide a direct demonstration of grid cells in the primate and suggest that EC neurons encode space during visual exploration, even without locomotion.

Primates explore the visual world through the use of saccadic eye movements. Neuronal activity in the hippocampus, a structure known to be essential for memory, is modulated by this saccadic activity, but the relationship between visual exploration through saccades and memory formation is not well understood. Here, we identify a link between theta-band (3-12 Hz) oscillatory activity in the hippocampus and saccadic activity in monkeys performing a recognition memory task. As monkeys freely explored novel images, saccades produced a theta-band phase reset, and the reliability of this phase reset was predictive of subsequent recognition. In addition, enhanced theta-band power before stimulus onset predicted stronger stimulus encoding. Together, these data suggest that hippocampal theta-band oscillations act in concert with active exploration in the primate and possibly serve to establish the optimal conditions for stimulus encoding.T he use of saccadic eye movements to acquire information about the surrounding environment is perhaps the most conspicuous example of exploratory behavior in the primate. This behavior provides a mechanism for parsing incoming information into discrete, stable segments (i.e., snapshots of individual elements comprising a complex visual scene, allowing time for sufficient processing to occur before moving to the next fixation target). This mechanism of actively sampling sensory information from the environment may be similar to the behaviors engaged in by rodents exploring their environment through such activities as sniffing and whisking. Specifically, the fixation period following each saccade may be homologous to the period of incoming sensory information accompanying each sniff cycle in the rodent (1). Recently, it has been suggested that motor behaviors associated with information gathering are integral to the "active sensing" process in natural behavior (2). It is plausible that there may exist certain common neuronal elements across species that are associated with active sensing processes, such that the neuronal mechanisms underlying the encoding of information are intimately connected with the motor activities involved in acquiring that information.In many mammalian species, voluntary, exploratory behaviors are often associated with theta-band activity, a prominent 3-to 12-Hz oscillatory activity in the hippocampus and other limbic structures. This activity has been studied extensively in the rodent hippocampus (3-5), but it has also been described in bats (6), cats (7), and, more recently, humans (8-11). In rodents, theta appears to show close temporal relationships with running (3, 12) and sniffing (13), suggesting an association between theta and the rate of sensory input. Although hippocampal theta has been identified in anesthetized monkeys (14), the lack of a clear demonstration of hippocampal theta in awake monkeys has been attributed to the fact that the recording methods typically require immobile, head-affixed monkeys, in contrast to rodent studies using freely moving ...

nant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. J Neurophysiol 98: 3525-3537, 2007. First published October 10, 2007 doi:10.1152/jn.00808.2007. Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

People often forget information because they fail to effectively encode it. Here, we test the hypothesis that targeted electrical stimulation can modulate neural encoding states and subsequent memory outcomes. Using recordings from neurosurgical epilepsy patients with intracranially implanted electrodes, we trained multivariate classifiers to discriminate spectral activity during learning that predicted remembering from forgetting, then decoded neural activity in later sessions in which we applied stimulation during learning. Stimulation increased encoding-state estimates and recall if delivered when the classifier indicated low encoding efficiency but had the reverse effect if stimulation was delivered when the classifier indicated high encoding efficiency. Higher encoding-state estimates from stimulation were associated with greater evidence of neural activity linked to contextual memory encoding. In identifying the conditions under which stimulation modulates memory, the data suggest strategies for therapeutically treating memory dysfunction.

In the suprachiasmatic nucleus (SCN), the master circadian pacemaker, neurons show circadian variations in firing frequency. There is also considerable synchrony of spiking across SCN neurons on a scale of milliseconds, but the mechanisms are poorly understood. Using paired whole-cell recordings, we have found that many neurons in the rat SCN communicate via electrical synapses. Spontaneous spiking was often synchronized in pairs of electrically coupled neurons, and the degree of this synchrony could be predicted from the magnitude of coupling. In wild-type mice, as in rats, the SCN contained electrical synapses, but electrical synapses were absent in connexin36-knockout mice. The knockout mice also showed dampened circadian activity rhythms and a delayed onset of activity during transition to constant darkness. We suggest that electrical synapses in the SCN help to synchronize its spiking activity, and that such synchrony is necessary for normal circadian behavior.