Eric Lowet

Boston University | BU · Department of Biology

Recent improvements in genetically encoded voltage indicators enabled optical imaging of action potentials and subthreshold transmembrane voltage in vivo. To perform high speed voltage imaging of many neurons simultaneously over a large anatomical area, widefield microscopy remains an essential tool. However, the lack of optical sectioning makes wi...

We performed five and ten kilohertz imaging of individual hippocampal neurons expressing SomArchon using a high-speed sCMOS camera. The ultrafast imaging speed allows for detailed characterization of action potential waveforms in hippocampal neurons.

Rhythmic neural network activity has been broadly linked to behavior. However, it is unclear how membrane potentials of individual neurons track behavioral rhythms, even though many neurons exhibit pace-making properties in isolated brain circuits. To examine whether single-cell voltage rhythmicity is coupled to behavioral rhythms, we focused on de...

Deep brain stimulation (DBS) is a promising neuromodulation therapy, but the neurophysiological mechanisms of DBS remain unclear. In awake mice, we performed high-speed membrane voltage fluorescence imaging of individual hippocampal CA1 neurons during DBS delivered at 40 Hz or 140 Hz, free of electrical interference. DBS powerfully depolarized soma...

Stepping movement is delta (1–4 Hz) rhythmic and depends on sensory inputs. Stepping-related delta-rhythmic neural activity is coupled to beta (10–30 Hz) frequency dynamics that are also prominent in sensorimotor circuits. We explored how beta-frequency sensory stimulation influences stepping and dorsal striatal regulation of stepping. We delivered...

Stepping movement is delta (1-4 Hz) rhythmic and depends on sensory inputs. In addition to delta rhythms, beta (10-30 Hz) frequency dynamics are also prominent in the motor circuits and are coupled to neuronal delta rhythms both at the network and the cellular levels. Since beta rhythms are broadly supported by cortical and subcortical sensorimotor...

Under in vivo conditions, CA1 pyramidal cells from the hippocampus display transitions from single spikes to bursts. It is believed that subthreshold hyperpolarization and depolarization, also known as down and up-states, play a pivotal role in these transitions. Nevertheless, a central impediment to correlating suprathreshold (spiking) and subthre...

Voltage imaging with cellular specificity has been made possible by advances in genetically encoded voltage indicators. However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines the signal-to-noise ratio and induces crosstalk betw...

Here we report SUPPORT (statistically unbiased prediction utilizing spatiotemporal information in imaging data), a self-supervised learning method for removing Poisson–Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatiotemporal neighboring pixels, even...

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetic...

Voltage imaging with cellular specificity has been made possible by the tremendous advances in genetically encoded voltage indicators (GEVIs). However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines signal-to-noise ratio (SNR) a...

Microsaccades (MSs) are commonly associated with spatially directed attention, but how they affect visual processing is still not clear. We studied MSs in a task in which the animal was randomly cued to attend to a target stimulus and ignore distractors, and it was rewarded for detecting a color change in the target. We found that the enhancement o...

Hippocampal network activity at theta frequencies (5-10Hz) is important for behavior. However, it remains unclear how behaviorally-relevant network theta rhythms arise and interact with cellular dynamics to dictate spike timing. We performed membrane voltage (Vm) imaging of individual CA1 pyramidal cells and parvalbumin interneurons with simultaneo...

Brain oscillations emerge during sensory and cognitive processes and have been classified into different frequency bands. Yet, even within the same frequency band and between nearby brain locations, the exact frequencies of brain oscillations can differ. These frequency differences (detuning) have been largely ignored and play little role in curren...

Hippocampal neurons generate either single spikes or stereotyped bursts of spikes known as complex spikes. Although single and complex spikes co-occur in the same neuron, their contribution to information processing remains unclear. We analyzed hippocampal CA1 neurons in awake mice and in behaving rats, combining cellular membrane voltage imaging w...

Deep brain stimulation (DBS) is a promising neuromodulation therapy that alters neural activity via intracranial electrical stimulation. However, the neurophysiological mechanisms of DBS remain largely unknown, because of the difficulty of obtaining cellular resolution recordings without electrical interference. Here, we performed high-speed membra...

Recent improvements in genetically encoded voltage indicators enabled high precision imaging of single neuron's action potentials and subthreshold membrane voltage dynamics in the mammalian brain. To perform high speed voltage imaging, widefield microscopy remains an essential tool to record activity from many neurons simultaneously over a large an...

Gamma oscillations are thought to play a key role in neuronal network function and neuronal communication, yet the underlying generating mechanisms have not been fully elucidated to date. At least partly, this may be due to the fact that even in simple network models of interconnected inhibitory (I) and excitatory (E) neurons, many parameters remai...

Cortical synchrony is theorized to contribute to communication between connected networks during executive functioning. To understand the functional role of neural synchrony in cognitive flexibility, we recorded from auditory cortex (AC) and medial prefrontal cortex (mPFC), while mice performed an auditory extinction learning task. We found that wh...

To interpret the environment, our brain must evaluate external stimuli against internal representations from past experiences. How primary (S1) and secondary (S2) somatosensory cortices process stimuli depending on recent experiences is unclear. Using simultaneous multi-area population imaging of projection neurons and focal optogenetic inactivatio...

Here we present experimentally-validated computational models of gamma rhythm and use these to investigate gamma oscillation instability. To this end, we extracted empirical constraints for PING (Pyramidal Interneuron Network Gamma) models from monkey single-unit and LFP responses recorded during contrast variation. These constraints implied weak r...

The reduced detectability of a target T2 following discrimination of a preceding target T1 in the attentional blink (AB) paradigm is classically interpreted as a consequence of reduced attention to T2 due to attentional allocation to T1. Here, we investigated whether AB was related to changes in microsaccade rate (MSR). We found a pronounced MSR si...

The last decade has seen the emergence of new views about the mechanisms underlying specificity (or, conversely, generalization) of visual skill learning. Here, we trained participants at orientation discrimination paradigm at a peripheral position to induce position and orientation specificity and to test its underlying mechanisms. Specifically, w...

Attention can be “covertly” directed without eye movements; yet, even during fixation, there are continuous microsaccades (MSs). In areas V4 and IT of macaques, we found that firing rates and stimulus representations were enhanced by attention but only following a MS toward the attended stimulus. The onset of neural attentional modulations was tigh...

Primates sample their visual environment actively through saccades and microsaccades (MSs). Saccadic eye movements not only modulate neural spike rates but might also affect temporal correlations (synchrony) among neurons. Neural synchrony plays a role in neural coding and modulates information transfer between cortical areas. The question arises o...

The 2 different ways of achieving synchrony explained schematically. (A) Synchrony is achieved through (periodic) resetting by an outside source. (B) Synchrony arises through mutual interactions. (C) When synchrony is determined by an outside resetting pulse, connection strength and detuning no longer influence synchrony, therefore the Arnold Tongu...

Arnold tongue characterization of simulated neural activity using a model network similar to that used in from Fig 3. The simulation used for this analysis contained a network with isotropically connected neurons (as in Fig 3 and panel A) with locally varying input strength. (A) In the transient period, coherence (quantified by the PLV; see Materia...

Distance-dependent effects on synchrony persist when sustained period is lengthened. The input to the neurons in the simulation used to generate was altered by lengthening the MS-modulation kernel. (A) The modified MS-modulation kernel with lengthened interval between MSs. (B) Stimulus input pattern shown to the network. (C–D) The same analysis as...

Experimental analysis of V1 MS-triggered TFR power for different MS intervals. Panels are population averages from 2 monkeys (12 sessions, 36 laminar probes). (A) Averaging only for MS intervals that were between 160 ms and 240 ms. Black line represents averaged eye speed. (B) The same as in panel A, but for MS intervals that were longer than 330 m...

Gamma-band effects during the sustained period stay intact when varying stimuli across saccades. (A) During each interval between MSs, the network was presented with one of 3 possible stimuli. The stimulus patterns were randomly selected, but no 2 successive stimuli were the same. (C–F) As in S1 Fig. MS, microsaccade. (PDF)

Supplementary information. (1) The effect of increasing MS interval time on the network model and on V1 LFP recording sites. (2) Simulations showing that MS-locked effects persist if stimulus changes after each MS. (3) Proposal of a general theoretical framework to understand MS-locked synchronization changes. (4) Discussion of the theory of weakly...

Arnold tongue characterization of LFP recorded in monkey V1. Based on the same dataset as the one used for Figs 4–6. Because connection strength and local input drive cannot be measured directly, interaction strength and detuning were used on the 2 axes (see above). LFP, local field potential. (PDF)

Setup of a V1-V2 model network with anisotropic connection patterns. (A) Left: schematic representation of the network with its 2 subnetworks. Neurons in the first subnetwork (V1; 40 × 40 RSs, 20 × 20 FSs) receive direct input and project to the second subnetwork (V2; 100 RSs, 25 FSs) and to themselves. Neurons in V2 only project locally, i.e., the...

Gamma-band synchronization coordinates brief periods of excitability in oscillating neuronal populations to optimize information transmission during sensation and cognition. Commonly, a stable, shared frequency over time is considered a condition for functional neural synchronization. Here, we demonstrate the opposite: instantaneous frequency modul...

Background: Fourier-based techniques are used abundantly in the analysis of electrophysiological data. However, these techniques are of limited value when the signal of interest is non-sinusoidal or non-periodic. New method: We present sliding window matching (SWM): a new data-driven method for discovering recurring temporal patterns in electrop...

Presentation on "25th Annual Computational Neuroscience Meeting: CNS-2016 " BMC Neuroscience 17, 112-113 (2016).

Synchronization or phase-locking between oscillating neuronal groups is considered to be important for coordination of information among cortical networks. Spectral coherence is a commonly used approach to quantify phase locking between neural signals. We systematically explored the validity of spectral coherence measures for quantifying synchroniz...

Supplementary Information and Simulation Codes. The supplementary file contains supplementary methods, including mathematical derivation of phase-locking strength between two-coupled phase-oscillators, a more detailed description of the modulation sidebands in the FFT induced by systematic frequency or amplitude fluctuations and more information ab...

ICGenealogy: towards a common topology of neuronal ion channel function and genealogy in model and experiment Ion channels are fundamental constituents determining the function of single neurons and neuronal circuits. To understand their complex interactions, the field of computational modeling has proven essential: since its emergence, thousands...

Neuronal gamma-band synchronization (25-90 Hz) in visual cortex appears sustained and stable during prolonged visual stimulation when investigated with conventional averages across trials. Yet, recent studies in macaque visual cortex have used single-trial analyses to show that both power and frequency of gamma oscillations exhibit substantial mome...

Fine-scale temporal organization of cortical activity in the gamma range (∼25-80Hz) may play a significant role in information processing, for example by neural grouping ('binding') and phase coding. Recent experimental studies have shown that the precise frequency of gamma oscillations varies with input drive (e.g. visual contrast) and that it can...

Current theories propose that coherence of oscilla-tory brain activity in the gamma band (30–80 Hz) constitutes an avenue for communication among remote neural populations. However, reports documenting stimulus dependency and time variability of gamma frequency suggest that distant neuronal populations may, at any one time, operate at different fre...

Local field potentials (LFPs) represent the relatively slow varying components of the neural signal, and their analysis is instrumental in understanding normal brain function. To be properly analyzed, this signal needs to be separated in its fundamental frequency bands. Recent studies have shown that empirical mode decomposition (EMD) can be exploi...