Faculty Bibliography

Neural oscillations have been measured and interpreted in multitudinous ways, with a variety of hypothesized functions in physiology, information processing and cognition. Much attention has been paid in recent years to gamma-band (30-100 Hz) oscillations and synchrony, with an increasing interest in 'high gamma' (>100 Hz) signals as mesoscopic measures of inter-regional communication. The biophysical origins of the measured variables are often difficult to precisely identify, however, making their interpretation fraught with pitfalls. Here we discuss how measurements of inter-regional gamma coherence can be prone to misinterpretation and suggest strategies for deciphering the roles that synchronized oscillations across brain networks may play in neural function.

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Synaptic inhibition, brought about by a rich variety of interneuron types that target different domains of principal cells and other interneurons, counters excitation, modulates the gain, timing, tuning, bursting properties of principal cell firing, and exerts selective filtering of synaptic excitation. At the network level, it allows for coordinating transient interactions among the principal cells to form cooperative assemblies for efficient transmission of information and routing of excitatory activity across networks, typically in the form of brain oscillations. Targeted expression of neuronal activity modulators, such as optogenetics, allow physiological identification and perturbation of specific interneuron subtypes. Combined with large-scale recordings or imaging techniques, these approaches facilitate our understanding of the multiple roles of inhibitory interneurons in shaping circuit functions. This article is part of a Special Issue entitled 'GABAergic signaling'.

Sleep occupies roughly one-third of our lives, yet the scientific community is still not entirely clear on its purpose or function. Existing data point most strongly to its role in memory and homeostasis: that sleep helps maintain basic brain functioning via a homeostatic mechanism that loosens connections between overworked synapses, and that sleep helps consolidate and re-form important memories. In this review, we will summarize these theories, but also focus on substantial new information regarding the relation of electrical brain rhythms to sleep. In particular, while REM sleep may contribute to the homeostatic weakening of overactive synapses, a prominent and transient oscillatory rhythm called "sharp-wave ripple" seems to allow for consolidation of behaviorally relevant memories across many structures of the brain. We propose that a theory of sleep involving the division of labor between two states of sleep-REM and non-REM, the latter of which has an abundance of ripple electrical activity-might allow for a fusion of the two main sleep theories. This theory then postulates that sleep performs a combination of consolidation and homeostasis that promotes optimal knowledge retention as well as optimal waking brain function.

High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation of the rhythm and the recruitment of spikes from pyramidal neurons are still poorly understood. Using intracellular, sharp electrode recordings in freely moving, drug-free mice, we observed consistent large depolarizations in CA1 pyramidal cells during sharp wave ripples, which are associated with ripple frequency fluctuation of the membrane potential ("intracellular ripple"). Despite consistent depolarization, often exceeding pre-ripple spike threshold values, current pulse-induced spikes were strongly suppressed, indicating that spiking was under the control of concurrent shunting inhibition. Ripple events were followed by a prominent afterhyperpolarization and spike suppression. Action potentials during and outside ripples were orthodromic, arguing against ectopic spike generation, which has been postulated by computational models of ripple generation. These findings indicate that dendritic excitation of pyramidal neurons during ripples is countered by shunting of the membrane and postripple silence is mediated by hyperpolarizing inhibition.

Advances in understanding the genetics and underlying pathology of the catastrophic childhood epilepsies are pointing toward treatments.

Inhibitory neurons in cortical circuits play critical roles in composing spike timing and oscillatory patterns in neuronal activity. These roles in turn require coherent activation of interneurons at different timescales. To investigate how the local circuitry provides for these activities, we applied resampled cross-correlation analyses to large-scale recordings of neuronal populations in the cornu ammonis 1 (CA1) and CA3 regions of the hippocampus of freely moving rats. Significant counts in the cross-correlation of cell pairs, relative to jittered surrogate spike-trains, allowed us to identify the effective couplings between neurons in CA1 and CA3 hippocampal regions on the timescale of milliseconds. In addition to putative excitatory and inhibitory monosynaptic connections, we uncovered prominent millisecond timescale synchrony between cell pairs, observed as peaks in the central 0 ms bin of cross-correlograms. This millisecond timescale synchrony appeared to be independent of network state, excitatory input, and gamma oscillations. Moreover, it was frequently observed between cells of differing putative interneuronal type, arguing against gap junctions as the sole underlying source. Our observations corroborate recent in vitro findings suggesting that inhibition alone is sufficient to synchronize interneurons at such fast timescales. Moreover, we show that this synchronous spiking may cause stronger inhibition and rebound spiking in target neurons, pointing toward a potential function for millisecond synchrony of interneurons in shaping and affecting timing in pyramidal populations within and downstream from the circuit.

Precisely how rhythms support neuronal communication remains obscure. We investigated interregional coordination of gamma oscillations using high-density electrophysiological recordings in the rat hippocampus and entorhinal cortex. We found that 30-80 Hz gamma dominated CA1 local field potentials (LFPs) on the descending phase of CA1 theta waves during navigation, with 60-120 Hz gamma at the theta peak. These signals corresponded to CA3 and entorhinal input, respectively. Above 50 Hz, interregional phase-synchronization of principal cell spikes occurred mostly for LFPs in the axonal target domain. CA1 pyramidal cells were phase-locked mainly to fast gamma (>100 Hz) LFP patterns restricted to CA1, which were strongest at the theta trough. While theta phase coordination of spiking across entorhinal-hippocampal regions depended on memory demands, LFP gamma patterns below 100 Hz in the hippocampus were consistently layer specific and largely reflected afferent activity. Gamma synchronization as a mechanism for interregional communication thus rapidly loses efficacy at higher frequencies.