Coupling of Sharp Wave Events between Zebrafish Hippocampal and Amygdala Homologs.

The mammalian hippocampus exhibits spontaneous sharp wave events (1-30 Hz) with an often-present superimposed fast ripple oscillation (120-220 Hz) to form a sharp wave ripple (SWR) complex. During slow-wave sleep or quiet restfulness, SWRs result from the sequential spiking of hippocampal cell assemblies initially activated during learned or imagined experiences. Additional cortical/subcortical areas exhibit SWR events that are coupled to hippocampal SWRs, and studies in mammals suggest that coupling may be critical for the consolidation and recall of specific memories.

Concept for intrathecal delivery of brain recording and stimulation device.

Neurological disorders are common, yet many neurological diseases don't have efficacious treatments. The protected nature of the brain both anatomically and physiologically through the blood brain barrier (BBB) make it exceptionally hard to access. Recent advancements in interventional approaches, like the Stentrode™, have opened the possibility of using the cerebral vasculature as a highway for minimally invasive therapeutic delivery to the brain.

The inhibitory control of traveling waves in cortical networks.

Propagating waves of activity can be evoked and can occur spontaneously in vivo and in vitro in cerebral cortex. These waves are thought to be instrumental in the propagation of information across cortical regions and as a means to modulate the sensitivity of neurons to subsequent stimuli. In normal tissue, the waves are sparse and tightly controlled by inhibition and other negative feedback processes.

Transcranial Alternating Current Stimulation (tACS) as a Treatment for Insomnia.

We investigated the effects of transcranial alternating stimulation (tACS) in patients with insomnia. Nine patients with chronic insomnia underwent two in-laboratory polysomnography, 2 weeks apart, and were randomized to receive tACS either during the first or second study. The stimulation was applied simultaneously and bilaterally at F3/M1 and F4/M2 electrodes (0.

High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice.

Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact.

Preparing Viable Hippocampal Slices from Adult Mice for the Study of Sharp Wave-ripples.

We describe a protocol for preparing acute brain slices which can produce robust hippocampal sharp wave-ripples (SWRs) . The protocol is optimized for its simplicity and reliability for the preparation of solutions, slicing, and recovery incubation. Most slices in almost every mouse prepared though the protocol expressed vigorous spontaneous SWRs for ~24 h, compared to the 20-30% viability from "standard" low sodium slicing protocols.

Inhibitory Parvalbumin Basket Cell Activity is Selectively Reduced during Hippocampal Sharp Wave Ripples in a Mouse Model of Familial Alzheimer's Disease.

Memory disruption in mild cognitive impairment (MCI) and Alzheimer's disease (AD) is poorly understood, particularly at early stages preceding neurodegeneration. In mouse models of AD, there are disruptions to sharp wave ripples (SWRs), hippocampal population events with a critical role in memory consolidation. However, the microcircuitry underlying these disruptions is under-explored.

Venlafaxine Stimulates an MMP-9-Dependent Increase in Excitatory/Inhibitory Balance in a Stress Model of Depression.

Emerging evidence suggests that there is a reduction in overall cortical excitatory to inhibitory balance in major depressive disorder (MDD), which afflicts ∼14%-20% of individuals. Reduced pyramidal cell arborization occurs with stress and MDD, and may diminish excitatory neurotransmission. Enhanced deposition of perineuronal net (PNN) components also occurs with stress.

Increased matrix metalloproteinase levels and perineuronal net proteolysis in the HIV-infected brain; relevance to altered neuronal population dynamics.

HIV-associated neurocognitive disorders (HAND) continue to persist despite effective control of viral replication. Although the mechanisms underlying HAND are poorly understood, recent attention has focused on altered neuronal population activity as a correlate of impaired cognition. However, while alterations in neuronal population activity in the gamma frequency range are noted in the setting of HAND, the underlying mechanisms for these changes is unclear.

Measuring Sharp Waves and Oscillatory Population Activity With the Genetically Encoded Calcium Indicator GCaMP6f.

GCaMP6f is among the most widely used genetically encoded calcium indicators for monitoring neuronal activity. Applications are at both the cellular and population levels. Here, we explore two important and under-explored issues.

Venlafaxine stimulates PNN proteolysis and MMP-9-dependent enhancement of gamma power; relevance to antidepressant efficacy.

Drugs that target monoaminergic transmission represent a first-line treatment for major depression. Though a full understanding of the mechanisms that underlie antidepressant efficacy is lacking, evidence supports a role for enhanced excitatory transmission. This can occur through two non-mutually exclusive mechanisms.

Disruption of perineuronal nets increases the frequency of sharp wave ripple events.

Hippocampal sharp wave ripples (SWRs) represent irregularly occurring synchronous neuronal population events that are observed during phases of rest and slow wave sleep. SWR activity that follows learning involves sequential replay of training-associated neuronal assemblies and is critical for systems level memory consolidation. SWRs are initiated by CA2 or CA3 pyramidal cells (PCs) and require initial excitation of CA1 PCs as well as participation of parvalbumin (PV) expressing fast spiking (FS) inhibitory interneurons.

'Blue' voltage-sensitive dyes for studying spatiotemporal dynamics in the brain: visualizing cortical waves.

Among many distinct contributions made by Amiram Grinvald's group, the "Blue dyes" is a special gift for visualizing cortical population neuronal activity. The excitation wavelength of blue dyes has minimal overlap with the absorption of hemoglobin, and hence has minimal pulsation artifacts. This advantage leads to high signal-to-noise ratio optical recordings of cortical activity, with sensitivity as good as that of local field potential recordings.

Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity.

Hebbian, or associative, forms of synaptic plasticity are considered the molecular basis of learning and memory. However, associative synaptic modifications, including long-term potentiation (LTP) and depression (LTD), can form positive feedback loops which must be constrained for neural networks to remain stable. One proposed constraint mechanism is metaplasticity, a process whereby synaptic changes shift the threshold for subsequent plasticity.

Emergence of dominant initiation sites for interictal spikes in rat neocortex.

Neuronal populations with unbalanced inhibition can generate interictal spikes (ISs), where each IS starts from a small initiation site and then spreads activation across a larger area. We used in vivo voltage-sensitive dye imaging to map the initiation site of ISs in rat visual cortex disinhibited by epidural application of bicuculline methiodide. Immediately after the application of bicuculline, the IS initiation sites were widely distributed over the entire disinhibited area.

Monitoring Population Membrane Potential Signals from Neocortex.

Voltage-sensitive dyes (VSDs) and optical imaging are useful tools for studying spatiotemporal patterns of population neuronal activity in cortex. Because fast VSDs respond to membrane potential changes with microsecond temporal resolution, these are better suited than calcium indicators for recording rapid neural signals. Here we describe methods for using a 464 element photodiode array and fast VSDs to record signals ranging from large scale network activity in brain slices and in vivo mammalian preparations with sensitivity comparable to local field potential (LFP) recordings.

5-HT3a Receptors Modulate Hippocampal Gamma Oscillations by Regulating Synchrony of Parvalbumin-Positive Interneurons.

Gamma-frequency oscillatory activity plays an important role in information integration across brain areas. Disruption in gamma oscillations is implicated in cognitive impairments in psychiatric disorders, and 5-HT3 receptors (5-HT3Rs) are suggested as therapeutic targets for cognitive dysfunction in psychiatric disorders. Using a 5-HT3aR-EGFP transgenic mouse line and inducing gamma oscillations by carbachol in hippocampal slices, we show that activation of 5-HT3aRs, which are exclusively expressed in cholecystokinin (CCK)-containing interneurons, selectively suppressed and desynchronized firings in these interneurons by enhancing spike-frequency accommodation in a small conductance potassium (SK)-channel-dependent manner.

Low-intensity electric fields induce two distinct response components in neocortical neuronal populations.

Low-intensity alternating electric fields applied to the scalp are capable of modulating cortical activity and brain functions, but the underlying mechanisms remain largely unknown. Here, we report two distinct components of voltage-sensitive dye signals induced by low-intensity, alternating electric fields in rodent cortical slices: a "passive component," which corresponds to membrane potential changes directly induced by the electric field; and an "active component," which is a widespread depolarization that is dependent on excitatory synaptic transmission. The passive component is stationary, with amplitude and phase accurately reflecting the cortical cytoarchitecture.

Priming with real motion biases visual cortical response to bistable apparent motion.

Apparent motion quartet is an ambiguous stimulus that elicits bistable perception, with the perceived motion alternating between two orthogonal paths. In human psychophysical experiments, the probability of perceiving motion in each path is greatly enhanced by a brief exposure to real motion along that path. To examine the neural mechanism underlying this priming effect, we used voltage-sensitive dye (VSD) imaging to measure the spatiotemporal activity in the primary visual cortex (V1) of awake mice.

The role of inhibition in oscillatory wave dynamics in the cortex.

Cortical oscillations arise during behavioral and mental tasks, and all temporal oscillations have particular spatial patterns. Studying the mechanisms that generate and modulate the spatiotemporal characteristics of oscillations is important for understanding neural information processing and the signs and symptoms of dynamical diseases of the brain. Nevertheless, it remains unclear how GABAergic inhibition modulates these oscillation dynamics.

Flow detection of propagating waves with temporospatial correlation of activity.

Voltage-sensitive dye imaging (VSDI) allows population patterns of cortical activity to be recorded with high temporal resolution, and recent findings ascribe potential significance to these spatial propagation patterns--both for normal cortical processing and in pathologies such as epilepsy. However, analysis of these spatiotemporal patterns has been mostly qualitative to date. In this report, we describe an algorithm to quantify fast local flow patterns of cortical population activation, as measured with VSDI.

Spiral wave dynamics in neocortex.

Although spiral waves are ubiquitous features of nature and have been observed in many biological systems, their existence and potential function in mammalian cerebral cortex remain uncertain. Using voltage-sensitive dye imaging, we found that spiral waves occur frequently in the neocortex in vivo, both during pharmacologically induced oscillations and during sleep-like states. While their life span is limited, spiral waves can modify ongoing cortical activity by influencing oscillation frequencies and spatial coherence and by reducing amplitude in the area surrounding the spiral phase singularity.

Propagating waves of activity in the neocortex: what they are, what they do.

The development of voltage-sensitive dyes (VSD) and fast optical imaging techniques have brought us a new tool for examining spatiotemporal patterns of population neuronal activity in the neocortex. Propagating waves have been observed during almost every type of cortical processing examined by VSD imaging or electrode arrays. These waves provide subthreshold depolarization to individual neurons and increase their spiking probability.

Crossmodal propagation of sensory-evoked and spontaneous activity in the rat neocortex.

In the cortex, neural responses to crossmodal stimulation are seen both in higher association areas and in primary sensory areas, and are thought to play a role in integration of crossmodal sensations. We used voltage-sensitive dye imaging (VSDI) to study the spatiotemporal characteristics of such crossmodal neural activity. We imaged three cortical regions in rat: primary visual cortex (V1), barrel field of primary somatosensory cortex (S1bf) and parietal association area (PA, flanked by V1 and S1bf).