A consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations
Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.
Inhibitory conductance controls place field dynamics in the hippocampus
Hippocampal place cells receive a disparate collection of excitatory and inhibitory currents that endow them with spatially selective discharges and rhythmic activity. Using a combination of inÂ vivo intracellular and extracellular recordings with opto/chemogenetic manipulations and computational modeling, we investigate the influence of inhibitory and excitatory inputs on CA1 pyramidal cell responses. At the cell bodies, inhibition leads and is stronger than excitation across the entire theta cycle. Pyramidal neurons fire on the ascending phase of theta when released from inhibition. Computational models equipped with the observed conductances reproduce these dynamics. In these models, place field properties are favored when the increased excitation is coupled with a reduction of inhibition within the field. As predicted by our simulations, firing rate within place fields and phase locking to theta are impaired by DREADDs activation of interneurons. Our results indicate that decreased inhibitory conductance is critical for place field expression.
Brain-implanted conductors amplify radiofrequency fields in rodents: advantages and risks
Neuronal activity under transcranial radio-frequency stimulation in metal-free rodent brains in-vivo
Action-driven remapping of hippocampal neuronal populations in jumping rats
The current dominant view of the hippocampus is that it is a navigation "device" guided by environmental inputs. Yet, a critical aspect of navigation is a sequence of planned, coordinated actions. We examined the role of action in the neuronal organization of the hippocampus by training rats to jump a gap on a linear track. Recording local field potentials and ensembles of single units in the hippocampus, we found that jumping produced a stereotypic behavior associated with consistent electrophysiological patterns, including phase reset of theta oscillations, predictable global firing-rate changes, and population vector shifts of hippocampal neurons. A subset of neurons ("jump cells") were systematically affected by the gap but only in one direction of travel. Novel place fields emerged and others were either boosted or attenuated by jumping, yet the theta spike phase versus animal position relationship remained unaltered. Thus, jumping involves an action plan for the animal to traverse the same route as without jumping, which is faithfully tracked by hippocampal neuronal activity.
Emerging principles of spacetime in brains: Meeting report on spatial neurodynamics
How do neurons and networks of neurons interact spatially? Here, we overview recent discoveries revealing how spatial dynamics of spiking and postsynaptic activity efficiently expose and explain fundamental brain and brainstem mechanisms behind detection, perception, learning, and behavior.
HectoSTAR Î¼LED Optoelectrodes for Large-Scale, High-Precision In Vivo Opto-Electrophysiology
Dynamic interactions within and across brain areas underlie behavioral and cognitive functions. To understand the basis of these processes, the activities of distributed local circuits inside the brain of a behaving animal must be synchronously recorded while the inputs to these circuits are precisely manipulated. Even though recent technological advances have enabled such large-scale recording capabilities, the development of the high-spatiotemporal-resolution and large-scale modulation techniques to accompany those recordings has lagged. A novel neural probe is presented in this work that enables simultaneous electrical monitoring and optogenetic manipulation of deep neuronal circuits at large scales with a high spatiotemporal resolution. The "hectoSTAR" micro-light-emitting-diode (Î¼LED) optoelectrode features 256 recording electrodes and 128 stimulation Î¼LEDs monolithically integrated on the surface of its four 30-Âµm thick silicon micro-needle shanks, covering a large volume with 1.3-mm Ã— 0.9-mm cross-sectional area located as deep as 6Â mm inside the brain. The use of this device in behaving mice for dissecting long-distance network interactions across cortical layers and hippocampal regions is demonstrated. The recording-and-stimulation capabilities hectoSTAR Î¼LED optoelectrodes enables will open up new possibilities for the cellular and circuit-based investigation of brain functions in behaving animals.
Brain-wide interactions during hippocampal sharp wave ripples
During periods of disengagement from the environment, transient population bursts, known as sharp wave ripples (SPW-Rs), occur sporadically. While numerous experiments have characterized the bidirectional relationship between SPW-Rs and activity in chosen brain areas, the topographic relationship between different segments of the hippocampus and brain-wide target areas has not been studied at high temporal and spatial resolution. Yet, such knowledge is necessary to infer the direction of communication. We analyzed two publicly available datasets with simultaneous high-density silicon probe recordings from across the mouse forebrain. We found that SPW-Rs coincide with a transient brain-wide increase in functional connectivity. In addition, we show that the diversity in SPW-R features, such as their incidence, magnitude, and intrahippocampal topography in the septotemporal axis, are correlated with slower excitability fluctuations in cortical and subcortical areas. Further, variations in SPW-R features correlated with the timing, sign, and magnitude of downstream responses with large-amplitude SPW-Rs followed by transient silence in extrahippocampal structures. Our findings expand on previous results and demonstrate that the activity patterns in extrahippocampal structures depend both on the intrahippocampal topographic origin and magnitude of hippocampal SPW-Rs.
Extrinsic control and intrinsic computation in the hippocampal CA1 circuit
In understanding circuit operations, a key problem is the extent to which neuronal spiking reflects local computation or responses to upstream inputs. We addressed this issue in the hippocampus by performing combined optogenetic and pharmacogenetic local and upstream inactivation. Silencing the medial entorhinal cortex (mEC) largely abolished extracellular theta and gamma currents in CA1 while only moderately affecting firing rates. In contrast, CA3 and local CA1 silencing strongly decreased firing of CA1 neurons without affecting theta currents. Each perturbation reconfigured the CA1 spatial map. However, the ability of the CA1 circuit to support place field activity persisted, maintaining the same fraction of spatially tuned place fields and reliable assembly expression as in the intact mouse. Thus, the CA1 network can induce and maintain coordinated cell assemblies with minimal reliance on its inputs, but these inputs can effectively reconfigure and assist in maintaining stability of the CA1 map.
Probing subthreshold dynamics of hippocampal neurons by pulsed optogenetics
Understanding how excitatory (E) and inhibitory (I) inputs are integrated by neurons requires monitoring their subthreshold behavior. We probed the subthreshold dynamics using optogenetic depolarizing pulses in hippocampal neuronal assemblies in freely moving mice. Excitability decreased during sharp-wave ripples coupled with increased I. In contrast to this "negative gain," optogenetic probing showed increased within-field excitability in place cells by weakening I and unmasked stable place fields in initially non-place cells. Neuronal assemblies active during sharp-wave ripples in the home cage predicted spatial overlap and sequences of place fields of both place cells and unmasked preexisting place fields of non-place cells during track running. Thus, indirect probing of subthreshold dynamics in neuronal populations permits the disclosing of preexisting assemblies and modes of neuronal operations.