152 research outputs found
Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice
Monitoring the membrane potential of individual neurons has uncovered how single-cell properties contribute to network processing across different brain states in neocortex. In contrast, the subthreshold modulation of hippocampal neurons by brain state has not been systematically characterized. To address this, we combined whole-cell recordings from dentate granule cells and CA1 pyramidal neurons with multisite extracellular recordings and behavioral measurements in awake mice. We show that the average membrane potential, amplitude of subthreshold fluctuations, and distance to spike threshold are all modulated by brain state. Furthermore, even within individual states, rapid variations in arousal are reflected in membrane potential fluctuations. These factors produce depolarizing ramps in the membrane potential of hippocampal neurons that precede ripples and mirror transitions to a network regime conducive for ripple generation. These results suggest that there are coordinated shifts in the subthreshold dynamics of individual neurons that underlie the transitions between distinct modes of hippocampal processing
Model-based spike sorting with a mixture of drifting t-distributions
Background:Chronic extracellular recordings are a powerful tool for systems neuroscience, but spike sorting remains a challenge. A common approach is to fit a generative model, such as a mixture of Gaussians, to the observed spike data. Even if non-parametric methods are used for spike sorting, such generative models provide a quantitative measure of unit isolation quality, which is crucial for subsequent interpretation of the sorted spike trains.
New method: We present a spike sorting strategy that models the data as a mixture of drifting t-distributions. This model captures two important features of chronic extracellular recordings—cluster drift over time and heavy tails in the distribution of spikes—and offers improved robustness to outliers.
Results: We evaluate this model on several thousand hours of chronic tetrode recordings and show that it fits the empirical data substantially better than a mixture of Gaussians. We also provide a software implementation that can re-fit long datasets in a few seconds, enabling interactive clustering of chronic recordings.
Comparison with existing methods: We identify three common failure modes of spike sorting methods that assume stationarity and evaluate their impact given the empirically-observed cluster drift in chronic recordings. Using hybrid ground truth datasets, we also demonstrate that our model-based estimate of misclassification error is more accurate than previous unit isolation metrics.
Conclusions: The mixture of drifting t-distributions model enables efficient spike sorting of long datasets and provides an accurate measure of unit isolation quality over a wide range of conditions
Structured Variability in Purkinje Cell Activity during Locomotion
The cerebellum is a prominent vertebrate brain structure that is critically involved in sensorimotor function. During locomotion, cerebellar Purkinje cells are rhythmically active, shaping descending signals and coordinating commands from higher brain areas with the step cycle. However, the variation in this activity across steps has not been studied, and its statistical structure, afferent mechanisms, and relationship to behavior remain unknown. Here, using multi-electrode recordings in freely moving rats, we show that behavioral variables systematically influence the shape of the step-locked firing rate. This effect depends strongly on the phase of the step cycle and reveals a functional clustering of Purkinje cells. Furthermore, we find a pronounced disassociation between patterns of variability driven by the parallel and climbing fibers. These results suggest that Purkinje cell activity not only represents step phase within each cycle but also is shaped by behavior across steps, facilitating control of movement under dynamic conditions
State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep
Cortico-hippocampal interactions during sleep are believed to reorganize neural circuits in support of memory consolidation. However, spike-timing relationships across cortico-hippocampal networks—key determinants of synaptic changes—are poorly understood. Here we show that cells in prefrontal cortex fire consistently within 100 ms after hippocampal cells in naturally sleeping animals. This provides evidence at the single cell-pair level for highly consistent directional interactions between these areas within the window of plasticity. Moreover, these interactions are state dependent: they are driven by hippocampal sharp-wave/ripple (SWR) bursts in slow-wave sleep (SWS) and are sharply reduced during REM sleep. Finally, prefrontal responses are nonlinear: as the strength of hippocampal bursts rises, short-latency prefrontal responses are augmented by increased spindle band activity and a secondary peak ∼100 ms later. These findings suggest that SWR events are atomic units of hippocampal-prefrontal communication during SWS and that the coupling between these areas is highly attenuated during REM sleep
Phase-locking of neurons in the hippocampus and the medial prefrontal cortex of the rat to the hippocampal theta rhythm
Thesis (Ph. D. in Neuroscience)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2005.Includes bibliographical references (p. 53-59).The interactions between cortical and hippocampal circuits are critical for memory formation, yet their basic organization at the neuronal network level is not well understood. Here we investigate the timing relationships between neuronal activity in the medial prefrontal cortex of freely behaving rats and the hippocampal theta rhythm. We demonstrate that a significant portion of prefrontal neurons are phase-locked to the hippocampal theta rhythm and we compare the phase-locking properties of prefrontal and hippocampal cells. We also show that prefrontal neurons phase-lock best to theta oscillations delayed by approximately 50 ms and confirm this hippocampo-prefrontal directionality and timing at the level of correlations between single cells. Finally we demonstrate that phase-locking of prefrontal cells is predicted by the presence of significant correlations with hippocampal cells at positive delays up to 150 ms, suggesting that direct hippocampal input has an important contribution to the observed prefrontal phase-locking. The theta entrained activity across cortico-hippocampal circuits described here may be important for gating information flow and guiding the plastic changes that are believed to underlie the storage of information across these networks.by Evgueniy V. Lubenov.Ph.D.in Neuroscienc
Nanofabricated Neural Probes for Dense 3-D Recordings of Brain Activity
Computations in brain circuits involve the coordinated activation of large populations of neurons distributed across brain areas. However, monitoring neuronal activity in the brain of intact animals with high temporal and spatial resolution has remained a technological challenge. Here we address this challenge by developing dense, three-dimensional (3-D) electrode arrays for electrophysiology. The 3-D arrays constitute the front-end of a modular and configurable system architecture that enables monitoring neuronal activity with unprecedented scale and resolution
Secure execution environment via program shepherding
Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (p. 77-82).We present program shepherding, a method for monitoring control flow transfers during program execution in order to enforce a security policy. Program shepherding provides three basic techniques as building blocks for security policies. First, program shepherding can restrict execution privileges on the basis of code origins. This distinction can ensure that malicious code masquerading as data is never executed, thwarting a large class of security attacks. Second, shepherding can restrict control transfers based on instruction type, source, and target. Finally, shepherding guarantees that sandboxing checks around any program operation will never be bypassed. Security attacks use inevitable bugs in trusted binaries to coerce a program into performing actions that it was never intended to perform. We use static and dynamic analyses to automatically build a custom security policy for a target program, which specifies the program's execution model. An accurate execution model restricts control flow transfers only to the intended ones and can thwart attacker attempts to alter program execution. For example, shepherding will allow execution of shared library code only through declared entry points. Finer specifications can be extracted from high-level information present in programs' source code - for example, which values a function pointer may take. Program shepherding will allow indirect calls only to their known targets, and function returns only to known callers. These analyses build a strict enough policy to prevent all deviations from the program's control flow graph and nearly all violations of the calling convention. This technique renders most security vulnerabilities unexploitable and thwarts current and future security attacks. We present an efficient implementation of program shepherding's capabilities in the DynamoRIO [6, 7] runtime code modification system. The resulting system imposes minimal performance overhead, operates on unmodified binaries, and requires no special hardware or operating system support.by Vladimir L. Kiriansky.M.Eng
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