Yonatan Katz

Shift in the Balance between Excitation and Inhibition during Sensory Adaptation of S1 Neurons

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.

Stochastic Emergence of Repeating Cortical Motifs in Spontaneous Membrane Potential Fluctuations In Vivo

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.

Cross-Whisker Adaptation of Neurons in the Rat Barrel Cortex

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.

Cortical Balance of Excitation and Inhibition Is Regulated by the Rate of Synaptic Activity

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 ∼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.

Intensity-Dependent Adaptation of Cortical and Thalamic Neurons Is Controlled by Brainstem Circuits of the Sensory Pathway

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.

Imbalance between excitation and inhibition in the somatosensory cortex produces postadaptation facilitation.

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.

Opposite adaptive processing of stimulus intensity in two major nuclei of the somatosensory brainstem.

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.

Neuronal adaptation in the somatosensory system of rodents

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.

Trial‐to‐trial correlation between thalamic sensory response and global EEG activity

Thalamic gating of sensory inputs to the cortex varies with behavioral conditions, such as sleep–wake 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 (1–4 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 (30–50 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.

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.