Biology subjects

Buzsaki, G.

Publications and source records attributed to Buzsaki, G..

45 records · Page 3Linked to original sources

bioRxiv2019

Cooling of medial septum reveals theta phase lag coordination of hippocampal cell assemblies

Hippocampal theta oscillations coordinate neuronal firing to support memory and spatial navigation. The medial septum (MS) is critical in theta generation by two possible mechanisms: either a unitary pacemaker timing signal is imposed on the hippocampal system or it may assist in organizing target subcircuits within the phase space of theta oscillations. We used temperature manipulation of the MS to test these models. Cooling of the MS reduced both theta frequency and power, was associated with enhanced incidence of errors in a spatial navigation task but did not affect spatial correlates of neurons. MS cooling decreased theta frequency oscillations of place cells, reduced distance-time compression but preserved distance-phase compression of place field sequences within the theta cycle. Thus, septal computation contributes not only theta pacing but is also critical for sustaining precise theta phase-coordination of cell assemblies in the hippocampus.

neuroscience↗

bioRxiv2019

Preexisting hippocampal network dynamics constrain optogenetically induced place fields

Neuronal circuits face a fundamental tension between maintaining existing structure and changing to accommodate new information. Memory models often emphasize the need to encode novel patterns of neural activity imposed by \"bottom-up\" sensory drive. In such models, learning is achieved through synaptic alterations, a process which potentially interferes with previously stored knowledge 1-3. Alternatively, neuronal circuits generate and maintain a preconfigured stable dynamic, sometimes referred to as an attractor, manifold, or schema 4-7, with a large reservoir of patterns available for matching with novel experiences 8-13. Here, we show that incorporation of arbitrary signals is constrained by pre-existing circuit dynamics. We optogenetically stimulated small groups of hippocampal neurons as mice traversed a chosen segment of a linear track, mimicking the emergence of place fields 1,14,15, while simultaneously recording the activity of stimulated and non-stimulated neighboring cells. Stimulation of principal neurons in CA1, but less so CA3 or the dentate gyrus, induced persistent place field remapping. Novel place fields emerged in both stimulated and non-stimulated neurons, which could be predicted from sporadic firing in the new place field location and the temporal relationship to peer neurons prior to the optogenetic perturbation. Circuit modification was reflected by altered spike transmission between connected pyramidal cell - inhibitory interneuron pairs, which persisted during post-experience sleep. We hypothesize that optogenetic perturbation unmasked sub-threshold, pre-existing place fields16,17. Plasticity in recurrent/lateral inhibition may drive learning through rapid exploration of existing states.

neuroscience↗

bioRxiv2019

Position-theta-phase model of hippocampal place cell activity applied to quantification of running speed modulation of firing rate

Spiking activity of place cells in the hippocampus encodes the animals position as it moves through an environment. Within a cells place field, both the firing rate and the phase of spiking in the local theta oscillation contain spatial information. We propose a position-theta-phase (PTP) model that captures the simultaneous expression of the firing-rate code and theta-phase code in place cell spiking. This model parametrically characterizes place fields to compare across cells, time and condition, generates realistic place cell simulation data, and conceptualizes a framework for principled hypothesis testing to identify additional features of place cell activity. We use the PTP model to assess the effect of running speed in place cell data recorded from rats running on linear tracks. For the majority of place fields we do not find evidence for speed modulation of the firing rate. For a small subset of place fields, we find firing rates significantly increase or decrease with speed. We use the PTP model to compare candidate mechanisms of speed modulation in significantly modulated fields, and determine that speed acts as a gain control on the magnitude of firing rate. Our model provides a tool that connects rigorous analysis with a computational framework for understanding place cell activity.\n\nSignificanceThe hippocampus is heavily studied in the context of spatial navigation, and the format of spatial information in hippocampus is multifaceted and complex. Furthermore, the hippocampus is also thought to contain information about other important aspects of behavior such as running speed, though there is not agreement on the nature and magnitude of their effect. To understand how all of these variables are simultaneously represented and used to guide behavior, a theoretical framework is needed that can be directly applied to the data we record. We present a model that captures well-established spatial-encoding features of hippocampal activity and provides the opportunity to identify and incorporate novel features for our collective understanding.

neuroscience↗

bioRxiv2019

Stimulation-artifact-free, high-spatiotemporal-resolution in vivo optoEphys with μLED optoelectrodes

The combination of in vivo extracellular recording and genetic-engineering-assisted optical stimulation is a powerful tool for the study of neuronal circuits. Precise analysis of complex neural circuits requires high-density integration of multiple cellular-size light sources and recording electrodes. However, high-density integration inevitably introduces stimulation artifact. We present minimal-stimulation-artifact (miniSTAR) {micro}LED optoelectrodes that enable effective elimination of stimulation artifact. A multi-metal-layer structure with a shielding layer effectively suppresses capacitive coupling of stimulation signals. A heavily-boron-doped silicon substrate silences the photovoltaic effect induced from LED illumination. With transient stimulation pulse shaping, we reduced stimulation artifact on miniSTAR {micro}LED optoelectrodes to below 50 {micro}Vpp, much smaller than a typical spike detection threshold, at optical stimulation of > 50 mW mm-2 irradiance. We demonstrated high-temporal resolution (< 1 ms) opto-electrophysiology without any artifact-induced signal quality degradation during in vivo experiments. MiniSTAR {micro}LED optoelectrodes will facilitate functional mapping of local circuits and discoveries in the brain.

bioengineering↗

bioRxiv2019

Routing of non-mnemonic hippocampal ripples to subcortical structures

The mnemonic functions of hippocampal sharp wave ripples (SPW-Rs) have been studied extensively. Because hippocampal outputs affect not only downsteam cortical structures but also subcortical targets, we examined the impact of SPW-Rs on the firing patterns of lateral septal (LS) neurons in behaving rats. A large fraction of SPW-Rs were temporally locked to high frequency oscillations (HFOs; 120-180 Hz) in LS. SPW-R to LS HFOs coupling was strongest during NREM sleep, followed by waking immobility. However, coherence and spike-LFP coupling between the two events were low, suggesting that HFOs are generated locally within the LS GABAergic population. This hypothesis was supported by optogenetic induction of HFOs in LS. Spiking of LS neurons was independent from the sequential order of spiking in SPW-Rs but, instead, correlated strongly with the magnitude of excitatory synchrony of the hippocampal output. Thus, LS is strongly activated by SPW-Rs and may convey hippocampal population events to its motivation and action-inducing targets in the hypothalamus and brainstem.

neuroscience↗

bioRxiv2018

Excitable dynamics of NREM sleep: a unifying model for neocortex and hippocampus

During non-rapid eye movement (NREM) sleep, the neocortex and hippocampus alternate between periods of neuronal spiking and inactivity. By directly comparing experimental observations with a mean field model of an adapting, recurrent neuronal population, we find that the neocortical alternations reflect a dynamical regime in which a stable active state is interrupted by transient inactive states (slow waves) while the hippocampal alternations reflect a stable inactive state interrupted by transient active states (sharp waves). We propose that during NREM sleep, hippocampal and neocortical populations are excitable: each in a stable state from which internal fluctuations or external perturbation can evoke the stereotyped population events that mediate NREM functions.

neuroscience↗

bioRxiv2017

Temporal coupling of field potentials and action potentials in the neocortex

The local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years investigators have found that action potential firing rates increase during elevations in power high-frequency band oscillations (50-200 Hz range). However action potentials also contribute to the LFP signal itself, making the spike-LFP relationship complex. Here we examine the relationship between spike rates and LFPs in varying frequency bands in rat neocortical recordings. We find that 50-180Hz oscillations correlate most consistently with high firing rates, but that other LFPs bands also carry information relating to spiking, including in some cases anti-correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation-based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.

neuroscience↗

bioRxiv2017

Cocaine place conditioning strengthens location-specific hippocampal inputs to the nucleus accumbens

Conditioned place preference (CPP) is a widely used model of addiction-related behavior whose underlying mechanism is not understood. In this study, we used dual site silicon probe recordings in freely moving mice to examine interactions between the hippocampus and nucleus accumbens in cocaine CPP. We found that CPP was associated with recruitment of nucleus accumbens medium spiny neurons to fire in the cocaine-paired location, and this recruitment was driven predominantly by selective strengthening of hippocampal inputs arising from place cells that encode the cocaine-paired location. These findings provide in vivo evidence that the synaptic potentiation in the accumbens caused by repeated cocaine administration preferentially affects inputs that were active at the time of drug exposure. This provides a potential physiological mechanism by which drug use becomes associated with specific environmental contexts.

neuroscience↗

bioRxiv2016

Sleep regulation of the distribution of cortical firing rates

Sleep is thought to mediate mnemonic and homeostatic functions. However, the mechanism by which this brain state can implement both the \"selective\" plasticity needed to consolidate novel memory traces as well as the \"general\" plasticity necessary to maintain a well-functioning neuronal system is unclear. Recent findings show that both of these functions differentially affect neurons based on their intrinsic firing rate, a ubiquitous neuronal heterogeneity. Furthermore, they are both implemented by the NREM slow oscillation, which also distinguishes neurons based on firing rate during sequential activity at the DOWN->UP transition. These findings suggest a mechanism by which spiking activity during the slow oscillation acts to maintain network statistics that promote a skewed distribution of neuronal firing rates, and \"perturbation\" of that activity by hippocampal replay acts to integrate new memory traces into the existing cortical network.

neuroscience↗