Biology subjects

Lampl, I.

Publications and source records attributed to Lampl, I..

11 recordsLinked to original sources

bioRxiv2025

Inherent coupling of perceptual judgments to actions in the mouse cortex

Neural activity during perceptual tasks is distributed across many cortical regions, but it remains unclear where perceptual judgments are made and whether they are encoded independently of the resulting actions. To address these questions, we designed a vibrotactile detection task in which mice flexibly switched between standard and reversed contingency blocks, requiring them to lick when a stimulus was present or absent, depending on the block. A cortex-wide optogenetic screen revealed that the premotor cortex is important for perceptual judgments rather than the ability to lick. However, coding of perceptual judgments in the premotor cortex and other cortical regions was coupled to actions rather than being independent of them. Finally, we identified a subset of premotor cortex cells whose activity encoded the current block identity. Based on these findings, we propose a model in which vibrotactile perceptual judgments are inherently, but flexibly, coupled to actions via cortical activity.

neuroscience↗

bioRxiv2022

Isolated correlates of somatosensory perception in the mouse posterior cortex

To uncover the neural correlates of stimulus perception, experimenters commonly use tasks in which subjects are repeatedly presented with a weak stimulus and instructed to report, via movement, if they perceived the stimulus. The difference in neural activity between reported stimulus (hit) and unreported stimulus (miss) trials is then seen as potentially perception-related. However, recent studies found that activity related to the report spreads throughout the brain, calling into question to what extent such tasks conflate perception-related activity with report-related activity. To isolate perception-related activity, we developed a paradigm in which the same mice were trained on both a regular go/no-go whisker stimulus detection task and a reversed contingencies version, in which they reported the absence of a whisker stimulus. By comparing no-report trials across the two tasks, we located perception-related activity within a posterior network of cortical regions contralateral to the stimulus. In addition, we found this activity was on average an order of magnitude lower than report-related activity and began after the low-level stimulus response. In summary, our study revealed the mouse cortical areas associated with the perception of a sensory stimulus independently of a perceptual report.

neuroscience↗

bioRxiv2021

A novel theoretical framework for simultaneous measurement of excitatory and inhibitory conductances

Firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system. ClassificationSystem Neuroscience, Cellular and Molecular Neuroscience

neuroscience↗

bioRxiv2020

Localized Chemogenetic Silencing of Inhibitory Neurons: A novel Mouse Model of Focal Cortical Seizures

Focal cortical epilepsies are frequently refractory to available anticonvulsant drug therapies. One key factor contributing to this state is the limited availability of animal models that allow to reliably study focal cortical seizures and how they recruit surrounding brain areas in-vivo. In this study, we selectively expressed the inhibitory chemogenetic receptor, hM4D, in GABAergic neurons in focal cortical areas using viral gene transfer. Following focal silencing of GABAergic neurons by administration of Clozapine-N-Oxide (CNO), we demonstrated reliable induction of local epileptiform events in the electroencephalogram (EEG) signal of awake freely moving mice. Experiments in anesthetized mice showed consistent induction of focal seizures in two different brain regions - the barrel cortex (BC) and at the medial prefrontal cortex (mPFC). Seizures were accompanied by high frequency oscillations, a known characteristic of human focal seizures. Seizures propagated, but an analysis of seizure propagation revealed favored propagation pathways. CNO-induced epileptiform events propagated from the BC on one hemisphere to its counterpart and from the BC to the mPFC, but not vice-versa. Lastly, post-CNO epileptiform events in the BC could be triggered by sensory whisker-pad stimulation, indicating that this model, applied to sensory cortices, may be useful to study sensory-evoked seizures. Taken together, our results show that targeted chemogenetic inhibition of GABAergic neurons using hM4D can serve as a novel, versatile and reliable model of focal cortical epilepsy suitable to systematically study cortical ictogenesis in different cortical areas. Significance StatementFocal cortical epilepsies are often hard to alleviate using current anticonvulsant therapies while further drug discovery is impeded by the limited variety of suitable animal models. In this study, we established a novel model of focal cortical seizures induced by spatially-restricted chemogenetic silencing of cortical inhibitory neurons. We have shown this method to be effective at various cortical regions and reliably induce seizures that share key characteristics with known human epilepsy traits, including sensory triggering and seizure propagation. This model may thus be used to advance the discovery of new remedies for focal cortical epilepsies, as well as to improve our understanding of seizure spread along different cortical pathways.

neuroscience↗

bioRxiv2019

Multiple timescales account for adaptive responses across sensory cortices

Sensory systems encounter remarkably diverse stimuli in the external environment. Natural stimuli exhibit timescales and amplitudes of variation that span a wide range. Mechanisms of adaptation, ubiquitous feature of sensory systems, allow for the accommodation of this range of scales. Are there common rules of adaptation across different sensory modalities? We measured the membrane potential responses of individual neurons in the visual, somatosensory and auditory cortices to discrete, punctate stimuli delivered at a wide range of fixed and nonfixed frequencies. We find that the adaptive profile of the response is largely preserved across these three areas, exhibiting attenuation and responses to the cessation of stimulation which are signatures of response to changes in stimulus statistics. We demonstrate that these adaptive responses can emerge from a simple model based on the integration of fixed filters operating over multiple time scales.

neuroscience↗

bioRxiv2019

Principles for simultaneous measurement of excitatory and inhibitory conductances of single cells in a single trial

Neuronal activity is determined by the interplay between excitatory and inhibitory inputs of individual cells. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs at the same time. Current methods for conductance measurement are based on repeatedly stimulating neurons while holding their membrane potential at different levels so to reveal either excitation or inhibition, which can only provide the averaged relationship between the two. Here we develop a new framework for simultaneously measuring both the excitatory and inhibitory inputs of single cells in a single trial under current clamp. This method is based on theoretical analysis of passive circuits and can be practically achieved by injecting a high frequency sinusoidal current and then analysing the data using an optimization algorithm. We use simulations to demonstrate the ability of this approach to reveal the excitatory and inhibitory inputs of point neurons, in which we mimic adapting sensory inputs as well as an asynchronous balanced state.

neuroscience↗

bioRxiv2019

Stereotactic system for accurately targeting deep brain structures in awake head-fixed mice

Deep brain nuclei, such as the amygdala, nucleus basalis, and locus coeruleus, play a crucial role in cognition and behavior. Nonetheless, acutely recording electrical activity from these structures in head-fixed awake rodents has been very challenging due to the fact that head-fixed preparations are not designed for stereotactic accuracy. We overcome this issue by designing the DeepTarget, a system for stereotactic head-fixation and recording, which allows for accurately directing recording electrodes or other probes into any desired location in the brain. We then validated it by performing intracellular recordings from optogenetically-tagged amygdalar neurons followed by histological reconstruction, which revealed that it is accurate and precise to within [~]100 m. Moreover, in another group of mice we were able to target both the mammillothalamic tract and subthalamic nucleus. This approach can be adapted to any type of extracellular electrode, fiber optic or other probe in cases where high accuracy is needed in awake, head-fixed rodents. Highlights> The Deep Target, new system for accurately targeting deep nuclei in head-fixed animals for electrophysiology and optogenetics. > Accurate and precise to within 100 m following a one-time alignment. > Validation: Opto-tagged Vm recordings in the amygdala of awake mice. > Validation: Targeting multiple deep brain structures in the same mouse.

neuroscience↗

bioRxiv2018

The correlated state in balanced neuronal networks

Understanding the magnitude and structure of inter-neuronal correlations and their relationship to synaptic connectivity structure is an important and difficult problem in computational neuroscience. Early studies show that neuronal network models with excitatory-inhibitory balance naturally create very weak spike train correlations. Later work showed that, under some connectivity structures, balanced networks can produce larger correlations between some neuron pairs, even when the average correlation is very small. All of these previous studies assume that the local neuronal network receives feedforward synaptic input from a population of uncorrelated spike trains. We show that when spike trains providing feedforward input are correlated, the downstream recurrent neuronal network produces much larger correlations. We provide an in-depth analysis of the resulting \"correlated state\" in balanced networks and show that, unlike the asynchronous state of previous work, it produces a tight excitatory-inhibitory balance consistent with in vivo cortical recordings.

neuroscience↗

bioRxiv2017

Membrane potential correlates of network decorrelation and improved SNR by cholinergic activation in the somatosensory cortex.

The nucleus basalis (NB) projects cholinergic axons to the cortex where they play a major role in arousal, attention and learning. Cholinergic inputs shift cortical dynamics from synchronous to asynchronous and improves the signal to noise ratio (SNR) of sensory response. Yet, the underlying mechanisms of these changes remain unclear. Using simultaneous extracellular and whole cell patch recordings in layer 4 barrel cortex we show that activation of the cholinergic system has a differential effect on ongoing and sensory evoked activities. Cholinergic activation eliminated the large and correlated spontaneous synaptic fluctuations in membrane potential while sparing the synaptic response to whisker stimulation. This differential effect of cholinergic activation provides a unified explanation for the increased SNR of sensory response and for the reduction in both trial to trial variability and noise correlations as well as explaining the shift into desynchronized cortical state which are the hallmarks of arousal and attention.

neuroscience↗

bioRxiv2017

High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

Optogenetic silencing allows time-resolved functional interrogation of defined neuronal populations. However, the limitations of inhibitory optogenetic tools impose stringent constraints on experimental paradigms. The high light power requirement of light-driven ion pumps and their effects on intracellular ion homeostasis pose unique challenges, particularly in experiments that demand inhibition of a widespread neuronal population in vivo. Guillardia theta anion-conducting channelrhodopsins (GtACRs) are promising in this regard, due to their high single-channel conductance and favorable photon-ion stoichiometry. However, GtACRs show poor membrane targeting in mammalian cells, and the activity of such channels can cause transient excitation in the axon due to an excitatory chloride reversal potential in this compartment. Here we address both problems by enhancing membrane targeting and subcellular compartmentalization of GtACRs. The resulting GtACR-based optogenetic tools show improved photocurrents, greatly reduced axonal excitation, high light sensitivity and rapid kinetics, allowing highly efficient inhibition of neuronal activity in the mammalian brain.

neuroscience↗

bioRxiv2017

Coupling Of Tactile LFP Signals Between Mouse Cortex And Olfactory Bulb

Local field potentials are an important measure of brain activity and have been used to address various mechanistic and behavioral questions. We revealed a prominent whisker evoked local field potential signal in the olfactory bulb and investigated its physiology. This signal, dependent on barrel cortex activation and highly correlated with its local activity, represented a pure volume conductance signal that was sourced back to the activity in the ventro-lateral orbitofrontal cortex, located a few millimeters away. Thus, we suggest that special care should be taken when acquiring and interpreting LFP data.

neuroscience↗