(2021) Nature Communications. 12, 1, 4095. Abstract
Interhemispheric correlation between homotopic areas is a major hallmark of cortical physiology and is believed to emerge through the corpus callosum. However, how interhemispheric correlations and corpus callosum activity are affected by behavioral states remains unknown. We performed laminar extracellular and intracellular recordings simultaneously from both barrel cortices in awake mice. We find robust interhemispheric correlations of both spiking and synaptic activities that are reduced during whisking compared to quiet wakefulness. Accordingly, optogenetic inactivation of one hemisphere reveals that interhemispheric coupling occurs only during quiet wakefulness, and chemogenetic inactivation of callosal terminals reduces interhemispheric correlation especially during quiet wakefulness. Moreover, in contrast to the generally elevated firing rate observed during whisking epochs, we find a marked decrease in the activity of imaged callosal fibers. Our results indicate that the reduction in interhemispheric coupling and correlations during active behavior reflects the specific reduction in the activity of callosal neurons.Interhemispheric correlations are mediated by the corpus callosum, an extensive fiber bundle connecting the cortical hemispheres. The authors show that interhemispheric correlations between the somatosensory cortices of awake mice are reduced during whisking as a result of lower callosal activity.
NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal’s behavioral state(2021) Neuron (Cambridge, Mass.). 109, 13, p. 2150-2164 Abstract[All authors]
Processing of sensory information in neural circuits is modulated by an animal’s behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state-dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1 NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1 NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain-modulate sensory processing in whole cortical columns.
(2021) Frontiers in Systems Neuroscience. 15, 646563. Abstract
Neurons in the barrel cortex respond preferentially to stimulation of one principal whisker and weakly to several adjacent whiskers. Such integration exists already in layer 4, the pivotal recipient layer of thalamic inputs. Previous studies show that cortical neurons gradually adapt to repeated whisker stimulations and that layer 4 neurons exhibit whisker specific adaptation and no apparent interactions with other whiskers. This study aimed to study the specificity of adaptation of layer 2/3 cortical cells. Towards this aim, we compared the synaptic response of neurons to either repetitive stimulation of one of two responsive whiskers or when repetitive stimulation of the two whiskers was interleaved. We found that in most layer 2/3 cells adaptation is whisker-specific. These findings indicate that despite the multi-whisker receptive fields in the cortex, the adaptation process for each whisker-pathway is mostly independent of other whiskers. A mechanism allowing high responsiveness in complex environments.
(2019) Journal of Neuroscience. 39, 50, p. 10019-10033 Abstract
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, a 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 of male and female mice 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.
(2019) Journal of Neuroscience Methods. 325, 108324. Abstract
Single cell intracellular recordings in-vivo at deep brain structures are seldomly accompanied by nearby optogenetics or drug application. The use of such tools is limited as both light and drugs cannot penetrate deep inside brain tissue. Hence, the optical fiber or drug delivery pipette needs to be placed within the brain close to the recording pipette. So far, however, this has required highly accurate hardware to achieve. These complications have now been solved by new approaches enabling intracellular recordings both for optogenetics and pharmacological application by the use of a single manipulator. In this manuscript we review these technologies - their pros, cons and implications.
(2019) Journal of Neurophysiology. 122, 3, p. 975-983 Abstract
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 similar to 100 mu 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, bead-fixed rodents.NEW & NOTEWORTHY Accurate targeting of recording electrodes in awake head-restrained rodents is currently beyond our reach. We developed a device for stereotactic implantation of a custom head bar and a recording system that together allow the accurate and precise targeting of any brain structure, including deep and small nuclei. We demonstrated this by performing histology and intracellular recordings in the amygdala of awake mice. The system enables the targeting of any probe to any location in the awake brain.
(2019) Physical Review E. 99, 5, 052414. Abstract
Understanding the magnitude and structure of interneuronal 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, defining the "asynchronous state." 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 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 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, it produces a tight excitatory-inhibitory balance consistent with in vivo cortical recordings.
(2018) Nature Communications. 9, 4125. Abstract
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 these problems by enhancing membrane targeting and subcellular compartmentalization of GtACRs. The resulting soma-targeted GtACRs show improved photocurrents, reduced axonal excitation and high light sensitivity, allowing highly efficient inhibition of neuronal activity in the mammalian brain.
(2017) Cell Reports. 21, 4, p. 919-925 Abstract
Local field potentials (LFPs) are an important measure of brain activity and have been used to address various mechanistic and behavioral questions. We revealed a prominent whisker-evoked LFP 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 conduction 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.
(2017) Neuroscience. 343, p. 66-76 Abstract
The sensory systems in animals constantly monitor the environment and process salient and relevant features while subtracting background activity. This process requires continuous recalibration of neuronal gain based on recent history. Adaptation has been postulated to be the key mechanism by which neurons rapidly tune their response curves to represent the entire dynamic range of external inputs. Rodents heavily rely on their vibrissa system while gathering information about their surroundings using whisking. Neuronal adaptation is observed in all stages of sensory processing, from the whisker follicle through the brainstem and thalamus up to the barrel cortex. In this review, we discuss the intrinsic, synaptic and network mechanisms of adaptation such as short-term synaptic depression, inhibitory suppression, balance between excitation and inhibition as well as the role of cascading adaptation. Furthermore, we describe recent findings about the different intensity dependent adaptation properties in the two major somatosensory pathways and their possible implications about coding. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
Simultaneous Bayesian Estimation of Excitatory and Inhibitory Synaptic Conductances by Exploiting Multiple Recorded Trials(2016) Frontiers in Computational Neuroscience. 10, 110. Abstract
Advanced statistical methods have enabled trial-by-trial inference of the underlying excitatory and inhibitory synaptic conductances (SCs) of membrane-potential recordings. Simultaneous inference of both excitatory and inhibitory SCs sheds light on the neural circuits underlying the neural activity and advances our understanding of neural information processing. Conventional Bayesian methods can infer excitatory and inhibitory SCs based on a single trial of observed membrane potential. However, if multiple recorded trials are available, this typically leads to suboptimal estimation because they neglect common statistics (of synaptic inputs (Sls)) across trials. Here, we establish a new expectation maximization (EM) algorithm that improves such single-trial Bayesian methods by exploiting multiple recorded trials to extract common SI statistics across the trials. In this paper, the proposed EM algorithm is embedded in parallel Kalman filters or particle filters for multiple recorded trials to integrate their outputs to iteratively update the common SI statistics. These statistics are then used to infer the excitatory and inhibitory SCs of individual trials. We demonstrate the superior performance of multiple-trial Kalman filtering (MtKF) and particle filtering (MtPF) relative to that of the corresponding single-trial methods. While relative estimation error of excitatory and inhibitory SCs is known to depend on the level of current injection into a cell, our numerical simulations using MtKF show that both excitatory and inhibitory SCs are reliably inferred using an optimal level of current injection. Finally, we validate the robustness and applicability of our technique through simulation studies, and we apply MtKF to in vivo data recorded from the rat barrel cortex.
(2016) Nat Commun. 7, 12740. Abstract
Thalamic inputs of cells in sensory cortices are outnumbered by local connections. Thus, it was suggested that robust sensory response in layer 4 emerges due to synchronized thalamic activity. To investigate the role of both inputs in the generation of correlated cortical activities, we isolated the thalamic excitatory inputs of cortical cells by optogenetically silencing cortical firing. In anaesthetized mice, we measured the correlation between isolated thalamic synaptic inputs of simultaneously patched nearby layer 4 cells of the barrel cortex. Here we report that in contrast to correlated activity of excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit lower variability and asynchronous spontaneous and sensory-evoked inputs. These results are further supported in awake mice when we recorded the excitatory inputs of individual cortical cells simultaneously with the local field potential in a nearby site. Our results therefore indicate that cortical synchronization emerges by intracortical coupling.
(2016) Frontiers in Systems Neuroscience. 10, 56. Abstract
Stimulus specific adaptation has been studied extensively in different modalities. High specificity implies that deviant stimulus induces a stronger response compared to a common stimulus. The thalamus gates sensory information to the cortex, therefore, the specificity of adaptation in the thalamus must have a great impact on cortical processing of sensory inputs. We studied the specificity of adaptation to whisker identity in the ventral posteromedial nucleus of the thalamus (VPM) in rats using extracellular and intracellular recordings. We found that subsequent to repetitive stimulation that induced strong adaptation, the response to stimulation of the same, or any other responsive whisker was equally adapted, indicating that thalamic adaptation is nonspecific. In contrast, adaptation of single units in the upstream brainstem principal trigeminal nucleus (PrV) was significantly more specific. Depolarization of intracellularly recorded VPM cells demonstrated that adaptation is not due to buildup of inhibition. In addition, adaptation increased the probability of observing complete synaptic failures to tactile stimulation. In accordance with short-term synaptic depression models, the evoked synaptic potentials in response to whisker stimulation, subsequent to a response failure, were facilitated. In summary, we show that local short-term synaptic plasticity is involved in the transformation of adaptation in the trigemino-thalamic synapse and that the low specificity of adaptation in the VPM emerges locally rather than cascades from earlier stages. Taken together we suggest that during sustained stimulation, local thalamic mechanisms equally suppress inputs arriving from different whiskers before being gated to the cortex.
Errata to "Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor" (vol 91, pg 560)(2016) Proceedings of the Japan Academy Series B: Physical and Biological Sciences. 92, 2, p. 76-76 Abstract
In this paper, the phrases should be corrected as follows:(page 575, ref. 20)For “parent”Read “trunk”(page 576, ref. 39)For “peroxidise”Read “peroxidase”[All authors]
Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor(2015) Proceedings of the Japan Academy Series B: Physical and Biological Sciences. 91, 10, p. 560-576 Abstract
This study focuses on the structure and function of the primary sensory neurons that innervate vibrissal follicles in the rat. Both the peripheral and central terminations, as well as their firing properties were identified using intracellular labelling and recording in trigeminal ganglia in vivo. Fifty-one labelled neurons terminating peripherally, as club-like, Merkel, lanceolate, reticular or spiny endings were identified by their morphology. All neurons responded robustly to air puff stimulation applied to the vibrissal skin. Neurons with club-like endings responded with the highest firing rates; their peripheral processes rarely branched between the cell body and their terminal tips. The central branches of these neurons displayed abundant collaterals terminating within all trigeminal nuclei. Analyses of three-dimensional reconstructions reveal a palisade arrangement of club-like endings bound to the ringwulst by collagen fibers. Our morphological findings suggest that neurons with club-like endings sense mechanical aspects related to the movement of the ringwulst and convey this information to all trigeminal nuclei in the brainstem.[All authors]
Faithful Representation of Tactile Intensity under Different Contexts Emerges from the Distinct Adaptive Properties of the First Somatosensory Relay Stations(2015) Journal of Neuroscience. 35, 18, p. 6997-7002 Abstract
Adaptation allows neurons to respond to a wide range of stimulus intensities. However, it also leads to ambiguity as the representation of the external world depends on the context. We recorded neurons from Wistar rats' brainstem nuclei belonging to two major somatosensory pathways (lemniscal and paralemniscal) and explored the way in which they encode noisy stimuli under different contexts. We found that although their unadapted intensity-response curves are very similar, the adapted curves of the two pathways are distinctively different as they are optimized for encoding different intensity ranges. Lemniscal neurons most faithfully encoded stimuli when the background intensity was high, whereas paralemniscal cells best encoded stimuli under low intensity context. Intracellular recordings indicate that these differences emerge already at the synaptic level. We suggest that the two pathways synergistically improve the ability of this system to encode a wide range of intensities during natural stimulation, potentially reducing the inherent ambiguity of adaptive coding.
Opposite Adaptive Processing of Stimulus Intensity in Two Major Nuclei of the Somatosensory Brainstem(2013) Journal of Neuroscience. 33, 39, p. 15394-15400 Abstract
Tactile information ascends from the brainstem to the somatosensory cortex via two major parallel pathways, lemniscal and paralemniscal. In both pathways, and throughout all processing stations, adaptation effects are evident. Although parallel processing of sensory information is not unique to this system, the distinct information carried by these adaptive pathways remains unclear. Using in vivo intracellular recordings at their divergence point (brainstem trigeminal complex) in rats, we found opposite adaptation effects in the corresponding nuclei of these two pathways. Increasing the intensity of vibrissa stimulation entailed more adaption in paralemniscal neurons, whereas it caused less adaptation in lemniscal cells. Furthermore, increasing the intensity sharpens lemniscal receptive field profile as adaptation progresses. We hypothesize that these pathways evolved to operate optimally at different dynamic ranges of sustained sensory stimulation. Accordingly, the two pathways are likely to serve different functional roles in the transmission of weak and strong inputs. Hence, our results suggest that due to the disparity in the adaptation properties of two major parallel pathways in this system, high and reliable throughput of information can be achieved at a wider range of stimulation intensities than by each pathway alone.
(2013) Journal of Neuroscience. 33, 36, p. 14359-14368 Abstract
Cortical activity is determined by the balance between excitation and inhibition. To examine how shifts in brain activity affect this balance, we recorded spontaneous excitatory and inhibitory synaptic inputs into layer 4 neurons from rat somatosensory cortex while altering the depth of anesthesia. The rate of excitatory and inhibitory events was reduced by similar to 50% when anesthesia was deepened. However, whereas both the amplitude and width of inhibitory synaptic events profoundly increased under deep anesthesia, those of excitatory events were unaffected. These effects were found using three different types of anesthetics, suggesting that they are caused by the network state and not by local specific action of the anesthetics. To test our hypothesis that the size of inhibitory events increased because of the decreased rate of synaptic activity under deep anesthesia, we blocked cortical excitation and replayed the slow and fast patterns of inhibitory inputs using intracortical electrical stimulation. Evoked inhibition was larger under low-frequency stimulation, and, importantly, this change occurred regardless of the depth of anesthesia. Hence, shifts in the balance between excitation and inhibition across distinct states of cortical activity can be explained by the rate of inhibitory inputs combined with their short-term plasticity properties, regardless of the actual global brain activity.
Imbalance between Excitation and Inhibition in the Somatosensory Cortex Produces Postadaptation Facilitation(2013) Journal of Neuroscience. 33, 19, p. 8463-8471 Abstract
Adaptation is typically associated with attenuation of the neuronal response during sustained or repetitive sensory stimulation, followed by a gradual recovery of the response to its baseline level thereafter. Here, we examined the process of recovery from sensory adaptation in layer IV cells of the rat barrel cortex using in vivo intracellular recordings. Surprisingly, in approximately one-third of the cells, the response to a test stimulus delivered a few hundred milliseconds after the adapting stimulation was significantly facilitated. Recordings under different holding potentials revealed that the enhanced response was the result of an imbalance between excitation and inhibition, where a faster recovery of excitation compared with inhibition facilitated the response. Hence, our data provide the first mechanistic explanation of sensory facilitation after adaptation and suggest that adaptation increases the sensitivity of cortical neurons to sensory stimulation by altering the balance between excitation and inhibition.
(2013) Proceedings of the National Academy of Sciences of the United States of America. 110, 14, p. 5665-5670 Abstract
The ability of the brain to adapt to environmental demands implies that neurons can change throughout life. The extent to which single neurons actually change remains largely unstudied, however. To evaluate how functional properties of single neurons change over time, we devised a way to perform in vivo time-lapse electrophysiological recordings from the exact same neuron. We monitored the contralateral and ipsilateral sensory-evoked spiking activity of individual L2/3 neurons from the somatosensory cortex of mice. At the end of the first recording session, we electroporated the neuron with a DNA plasmid to drive GFP expression. Then, 2 wk later, we visually guided a recording electrode in vivo to the GFP-expressing neuron for the second time. We found that contralateral and ipsilateral evoked responses (i.e., probability to respond, latency, and preference), and spontaneous activity of individual L2/3 pyramidal neurons are stable under control conditions, but that this stability could be rapidly disrupted. Contralateral whisker deprivation induced robust changes in sensory-evoked response profiles of single neurons. Our experiments provide a framework for studying the stability and plasticity of single neurons over long time scales using electrophysiology.
Optopatcher-An electrode holder for simultaneous intracellular patch-clamp recording and optical manipulation(2013) Journal of Neuroscience Methods. 214, 1, p. 113-117 Abstract
Optogenetics has rapidly become a standard method in neuroscience research. Although significant progress has been made in the development of molecular tools, refined techniques for combined light delivery and recording in vivo are still lacking. For example, simultaneous intracellular recording and light stimulation have only been possible by using two separate positioning systems. To overcome this limitation, we have developed a glass pipette holder which contains an additional port for the insertion of an optical fiber into the pipette. This device, which we called "optopatcher allows whole cell patch-clamp recording simultaneously with direct projection of light from the recording pipette. The holder spares the use of an additional manipulator and, importantly, enables accurate, stable and reproducible illumination. In addition, replacement of standard pipettes is done as easily as with the available commercial holders. Here we used the optopatcher in vivo to record the membrane potential of neurons from different cortical layers in the motor cortex of transgenic mice expressing channelrhodopsin-2 under the Thy1 promoter. We demonstrate the utility of the optopatcher by recording LFP and intracellular responses to light stimulation. (C) 2013 Elsevier B.V. All rights reserved.
(2012) European Journal of Neuroscience. 35, 6, p. 826-837 Abstract
Thalamic gating of sensory inputs to the cortex varies with behavioral conditions, such as sleepwake cycles, or with different stages of anesthesia. Behavioral conditions in turn are accompanied by stereotypic spectral content of the EEG. In the rodent somatosensory system, the receptive field size of the ventral posteromedial thalamic nucleus (VPM) shrinks when anesthesia is deepened. Here we examined whether evoked thalamic responses are correlated with global EEG activity on a fine time scale of a few seconds. Trial-by-trial analysis of responses of VPM cells to whisker stimulation in lightly anesthetized rats indicated that increased EEG power in the delta band (14 Hz) was accompanied by a small, but highly significant, reduction in spontaneous and evoked thalamic firing. The opposite effect was found for the gamma EEG band (3050 Hz). These significant correlations were not accompanied by an apparent change in the size of the receptive fields and were not EEG phase-related. The correlation between EEG and firing rate was observed only in neurons that responded to multiple whiskers and was higher for the non-principal whiskers. Importantly, the contributions of the two EEG bands to the modulation of VPM responses were to a large extent independent of each other. Our findings suggest that information conveyed by different whiskers can be rapidly modulated according to the global brain activity.
(2010) Journal of Neurophysiology. 104, 5, p. 2615-2623 Abstract
Priebe NJ, Lampl I, Ferster D. Mechanisms of direction selectivity in cat primary visual cortex as revealed by visual adaptation. J Neurophysiol 104: 2615-2623, 2010. First published August 25, 2010; doi:10.1152/jn.00241.2010. In contrast to neurons of the lateral geniculate nucleus (LGN), neurons in the primary visual cortex (V1) are selective for the direction of visual motion. Cortical direction selectivity could emerge from the spatiotemporal configuration of inputs from thalamic cells, from intracortical inhibitory interactions, or from a combination of thalamic and intracortical interactions. To distinguish between these possibilities, we studied the effect of adaptation (prolonged visual stimulation) on the direction selectivity of intracellularly recorded cortical neurons. It is known that adaptation selectively reduces the responses of cortical neurons, while largely sparing the afferent LGN input. Adaptation can therefore be used as a tool to dissect the relative contribution of afferent and intracortical interactions to the generation of direction selectivity. In both simple and complex cells, adaptation caused a hyperpolarization of the resting membrane potential (-2.5 mV, simple cells, -0.95 mV complex cells). In simple cells, adaptation in either direction only slightly reduced the visually evoked depolarization; this reduction was similar for preferred and null directions. In complex cells, adaptation strongly reduced visual responses in a direction-dependent manner: the reduction was largest when the stimulus direction matched that of the adapting motion. As a result, adaptation caused changes in the direction selectivity of complex cells: direction selectivity was reduced after preferred direction adaptation and increased after null direction adaptation. Because adaptation in the null direction enhanced direction selectivity rather than reduced it, it seems unlikely that inhibition from the null direction is the primary mechanism for creating dir
Intensity-Dependent Adaptation of Cortical and Thalamic Neurons Is Controlled by Brainstem Circuits of the Sensory Pathway(2010) Neuron. 66, 2, p. 273-286 Abstract
Current views of sensory adaptation in the rat somatosensory system suggest that it results mainly from short-term synaptic depression. Experimental and theoretical studies predict that increasing the intensity of sensory stimulation, followed by an increase in firing probability at early sensory stages, is expected to attenuate the response at later stages disproportionately more than weaker stimuli, due to greater depletion of synaptic resources and the relatively slow recovery process. This may lead to coding ambiguity of stimulus intensity during adaptation. In contrast, we found that increasing the intensity of repetitive whisker stimulation entails less adaptation in cortical neurons. In a series of recordings, from the trigeminal ganglion to the thalamus, we pinpointed the source of the unexpected pattern of adaptation to the brainstem trigeminal complex. We suggest that low-level sensory processing counterbalances later effects of short-term synaptic depression by increasing the throughput of high-intensity sensory inputs
The Subthreshold Relation between Cortical Local Field Potential and Neuronal Firing Unveiled by Intracellular Recordings in Awake Rats(2010) Journal of Neuroscience. 30, 12, p. 4440-4448 Abstract
In most of the in vivo electrophysiological studies of cortical processing, which are extracellular, the spike-triggered local field potential average (LFP STA) is the measure used to estimate the correlation between the synaptic inputs of individual neuron and the local population. To understand how the magnitude and shape of LFP STA reflect the underlying correlation of synaptic activities, the membrane potential of the firing neuron has to be recorded together with the LFP. Using intracellular recordings from the cortex of awake rats, we found that for a large range of firing rates and for different behavioral states, the LFP STA represents both in its waveform and its magnitude the cross-correlation between the membrane potential of the neuron and the LFP. This data, supported by further analysis, suggests that LFP STA does not represent large network events specific to the spike times, but rather the synchrony between the mean synaptic activity of the population and the membrane potential of the single neuron, present both around spike times and in the intervals between spikes. Furthermore, it introduces a novel interpretation of the available data from unit and LFP extracellular recording experiments.
(2009) Neuron. 64, 6, p. 778-780 Abstract
In this issue of Neuron, Busse et al. describe the population response to superimposed visual stimuli while Sit et al. examine the spatiotemporal evolution of cortical activation in response to small visual stimuli. Surprisingly, these two studies of V1 report that a single gain control model accounts for their results.
(2009) Coherent Behavior In Neuronal Networks. p. 1-16 (1Springer Series in Computational Neuroscience). Abstract
In this chapter, we provide an overview of the dynamical properties of spontaneous activity in the cortex, as represented by the subthreshold membrane potential fluctuations of the cortical neurons. First, we discuss the main findings from various intracellular recording studies performed in anesthetized animals as well as from a handful of Studies in awake animals. Then, we focus on two specific questions pertaining to random and deterministic properties of cortical spontaneous activity. One of the questions is the relationship between excitation and inhibition, which is shown to posses a well-defined structure, owing to the spatio-temporal organization of the spontaneous activity in local cortical circuits at the millisecond scale. The other question regards the spontaneous activity at a scale of seconds and minutes. Here, examination of repeating patterns in subthreshold voltage fluctuations failed to reveal any evidence for deterministic structures.
(2008) Journal of Neuroscience. 28, 49, p. 13320-13330 Abstract
Sustained stimulation of sensory organs results in adaptation of the neuronal response along the sensory pathway. Whether or not cortical adaptation affects equally excitation and inhibition is poorly understood. We examined this question using patch recordings of neurons in the barrel cortex of anesthetized rats while repetitively stimulating the principal whisker. We found that inhibition adapts more than excitation, causing the balance between them to shift toward excitation. A comparison of the latency of thalamic firing and evoked excitation and inhibition in the cortex strongly suggests that adaptation of inhibition results mostly from depression of inhibitory synapses rather than adaptation in the firing of inhibitory cells. The differential adaptation of the evoked conductances that shifts the balance toward excitation may act as a gain mechanism which enhances the subthreshold response during sustained stimulation, despite a large reduction in excitation.
(2008) Nature Neuroscience. 11, 5, p. 535-537 Abstract
Temporal and quantitative relations between excitatory and inhibitory inputs in the cortex are central to its activity, yet they remain poorly understood. In particular, a controversy exists regarding the extent of correlation between cortical excitation and inhibition. Using simultaneous intracellular recordings in pairs of nearby neurons in vivo, we found that excitatory and inhibitory inputs are continuously synchronized and correlated in strength during spontaneous and sensory-evoked activities in the rat somatosensory cortex.
Rhythmic episodes of subthreshold membrane potential oscillations in the rat inferior olive nuclei in vivo(2007) Journal of Neuroscience. 27, 19, p. 5043-5052 Abstract
In vitro studies of inferior olive neurons demonstrate that they are intrinsically active, generating periodic spatiotemporal patterns. These self-generated patterns of activity extend the role of olivary neurons beyond that of a deliverer of teaching or error signals. However, autorhythmicity or patterned activity of complex spikes in the cerebellar cortex was observed in only a few studies. This discrepancy between the self-generated rhythmicity in the inferior olive observed in vitro and the sporadic reports on rhythmicity of complex spikes can be reconciled by recording intracellularly from inferior olive neurons in situ. To this end, we recorded intracellularly from olivary neurons of anesthetized rats. We demonstrate that, in vivo, olivary neurons show both slow and fast rhythmic processes. The slow process (0.2-2 Hz) is expressed as rhythmic transitions from quiescent periods to periods of fast rhythm, manifested as subthreshold oscillations of 6-12 Hz. Spikes, if they occur, are locked to the depolarized phase of these subthreshold oscillations and, therefore, hold and transfer rhythmic information. The transient nature of these oscillatory epochs accounts for the difficulties to uncover them by prolonged recordings of complex spikes activity in the cerebellar cortex.
Stochastic emergence of repeating cortical motifs in spontaneous membrane potential fluctuations in vivo(2007) Neuron. 53, 3, p. 413-425 Abstract
It was recently discovered that subthreshold membrane potential fluctuations of cortical neurons can precisely repeat during spontaneous activity, seconds to minutes apart, both in brain slices and in anesthetized animals. These repeats, also called cortical motifs, were suggested to reflect a replay of sequential neuronal firing patterns. We searched for motifs in spontaneous activity, recorded from the rat barrel cortex and from the cat striate cortex of anesthetized animals, and found numerous repeating patterns of high similarity and repetition rates. To test their significance, various statistics were compared between physiological data and three different types of stochastic surrogate data that preserve dynamical characteristics of the recorded data. We found no evidence for the existence of deterministically generated cortical motifs. Rather, the stochastic properties of cortical motifs suggest that they appear by chance, as a result of the constraints imposed by the coarse dynamics of subthreshold ongoing activity.
(2006) Journal of Neuroscience. 26, 51, p. 13363-13372 Abstract
Neurons in the barrel cortex and the thalamus respond preferentially to stimulation of one whisker ( the principal whisker) and weakly to several adjacent whiskers. Cortical neurons, unlike thalamic cells, gradually adapt to repeated whisker stimulations. Whether cortical adaptation is specific to the stimulated whisker is not known. The aim of this intracellular study was to determine whether the response of a cortical cell to stimulation of an adjacent whisker would be affected by previous adaptation induced by stimulation of the principal whisker and vice versa. Using a high-frequency stimulation that causes substantial adaptation in the cortex and much less adaptation in the thalamus, we show that cortical adaptation evoked by a train of stimuli applied to one whisker does not affect the synaptic response to subsequent stimulation of a neighboring whisker. Our data indicate that intrinsic mechanisms are not involved in cortical adaptation. Thalamic recordings obtained under the same conditions demonstrated that an adjacent whisker response was not generated in the thalamus, indicating that the observed whisker- specific adaptation results from diverging thalamic inputs or from cortical integration.
Intracellular measurements of spatial integration and the MAX operation in complex cells of the cat primary visual cortex(2004) Journal of Neurophysiology. 92, 5, p. 2704-2713 Abstract
We have examined the spatial integration properties of complex cells to determine whether some of their responses can be described by a maximum operation (MAX)-like computation, as suggested by Riesenhuber and Poggio's model of object recognition. Membrane potential was recorded from anesthetized cats while optimally oriented bars were presented, either alone or in pairs, in different parts of the cells' receptive field. In most cells, the membrane potential response to two bars presented simultaneously could not be predicted by the sum of the responses to individual bars. In many cells, however, the responses closely approximated a MAX-like model. That is, the response of the cell to two bars was similar to the larger of the two individual responses ("soft-MAX"). The degree of nonlinear summation varied from cell to cell and varied within single cells from one stimulus configuration to another but on average fit most closely to the MAX model. The firing response of the cells was also well predicted by the MAX-like model. The MAX-like behavior was independent of the distance between the bars (orthogonal to the preferred orientation), independent of the relative amplitude of the responses, and slightly less pronounced at low levels of contrast. This MAX-like behavior of a subset of complex cells may play an important role in invariant object recognition in clutter.