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Priebe, N. J.

Publications and source records attributed to Priebe, N. J..

12 recordsLinked to original sources

Parvalbumin and somatostatin inhibitory microcircuits perform distinct roles in stereo matching

We readily perceive stereoscopic depth in correlated random dot stereograms (RDS), in which every dot presented to one eye has a matching dot in the other eye. In contrast, anti-correlated RDS, in which corresponding dots have opposite contrast polarity between the two eyes, do not evoke a perception of depth. Nevertheless, anti-correlated RDS still generate local same-polarity matches within the receptive fields of individual neurons. Inhibitory circuitry has been proposed to suppress these false matches and thereby prevent the perception of illusory depth. To investigate how inhibitory circuits in visual cortex contribute to this process, we measured disparity selectivity to correlated and anti-correlated RDS in two major classes of inhibitory neurons in mice: parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) neurons. We found that the disparity tuning of PV+ neurons was highly correlated with the average activity of surrounding neurons. In contrast, the disparity tuning of SST+ neurons was poorly predicted by local population activity, suggesting that PV+ and SST+ neurons integrate excitatory inputs through distinct mechanisms. Optogenetic suppression of PV+ or SST+ neurons further revealed divergent functional roles. Although both cell types contributed to sharpening selectivity for correlated RDS, only SST+ neurons reduced selectivity for anti-correlated RDS. These findings suggest that PV+ and SST+ circuits both enhance responses to correct binocular matches in correlated RDS, whereas SST+ circuits contribute to suppressing false matches in anti-correlated RDS.

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The fluctuation-based regime of thalamocortical circuitry

Neocortical neurons in primary visual cortex (V1) integrate excitatory inputs from both thalamic and cortical sources to generate selectivity for orientation, direction and disparity. Feedforward models have posited that thalamocortical input can drive these selectivities, but the relative sparsity of thalamic synapses raises questions about the sufficiency of this input. To determine whether thalamic drive is sufficient to evoke cortical responses, we quantified the current threshold required to evoke action potentials in vivo using whole-cell recordings in mouse V1. We then isolated thalamic input via optogenetic cortical silencing and compared its strength to the measured spiking threshold. We find that although average thalamic input is below the threshold for action potential generation, trial-by-trial fluctuations in thalamic drive are sufficient to evoke visually driven action potentials. These results demonstrate that thalamic excitation alone can drive cortical spiking, but its effectiveness depends on fluctuations in synaptic input.

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Impaired thalamic burst firing in Fragile X syndrome

The thalamus performs a critical role in sensory processing by gating the flow of sensory information to the neocortex and directing sensory-driven behaviors; functions which are disrupted in people with autism spectrum disorders (ASD). We have identified cellular changes in thalamic neurons in a mouse model of Fragile X syndrome (FX), the leading monogenic cause of ASD, that alter how the thalamus transmits sensory information to neocortical circuits. In awake animals, thalamic relay cells gate input by shifting between two firing modes: burst and tonic. Relay cells in FX mice, however, do not shift between these modes and instead operate primarily in the tonic mode. We demonstrate that the lack of burst mode firing is caused by a shift in the voltage sensitivity for the Ca2+-dependent low threshold spike, which underlies normal burst firing.

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Luminance invariant encoding in primary visual cortex

The retina maintains sensitivity over a large range of luminance intensities by switching between rod and cone photoreceptors. This luminance adaptation has been shown to alter the receptive fields and interneuronal correlations of retinal ganglion cells (RGCs). While these adaptations allow the retina to encode visual information across environmental conditions, they present a challenge to downstream processing areas for which it is important that representations are invariant to light level. We measured the effects of scotopic versus photopic luminance adaptation on thalamic and cortical activity by tracking neuronal populations across light levels. While changes in the output of the retina are evident in the lateral geniculate nucleus (LGN), the representation in primary visual cortex (V1) is largely invariant to the changes in luminance. We show that an invariant V1 code can emerge through the integration of parallel functional pathways at the geniculocortical synapse.

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Interactions between saccades and smooth pursuit eye movements in marmosets

Animals use a combination of eye movements to track moving objects. These different eye movements need to be coordinated for successful tracking, requiring interactions between the systems involved. Here, we study the interaction between the saccadic and smooth pursuit eye movement systems in marmosets. Using a single target pursuit task, we show that saccades cause an enhancement in pursuit following a saccade. Using a two-target pursuit task, we show that this enhancement in pursuit is selective towards the motion of the target selected by the saccade, irrespective of any biases in pursuit prior to the saccade. These experiments highlight the similarities in the functioning of saccadic and smooth pursuit eye movement systems across primates. SIGNIFICANCE STATEMENTWe study the coordination between the smooth-pursuit and saccadic eye movement systems in marmosets using single and multiple object motions. We find that saccade to a target increases pursuit velocity towards the target. If multiple objects are visible, saccade choice makes pursuit more selective towards the saccade target. Our results show that coordination between different eye movement systems to successfully track moving objects is similar between marmosets and primates.

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Exact analysis of the subthreshold variability for conductance-based neuronal models with synchronous synaptic inputs

The spiking activity of neocortical neurons exhibits a striking level of variability, even when these networks are driven by identical stimuli. The approximately Poisson firing of neurons has led to the hypothesis that these neural networks operate in the asynchronous state. In the asynchronous state neurons fire independently from one another, so that the probability that a neuron experience synchronous synaptic inputs is exceedingly low. While the models of asynchronous neurons lead to observed spiking variability, it is not clear whether the asynchronous state can also account for the level of subthreshold membrane potential variability. We propose a new analytical framework to rigorously quantify the subthreshold variability of a single conductance-based neuron in response to synaptic inputs with prescribed degrees of synchrony. Technically we leverage the theory of exchangeability to model input synchrony via jump-process-based synaptic drives; we then perform a moment analysis of the stationary response of a neuronal model with all-or-none conductances that neglects post-spiking reset. As a result, we produce exact, interpretable closed forms for the first two stationary moments of the membrane voltage, with explicit dependence on the input synaptic numbers, strengths, and synchrony. For biophysically relevant parameters, we find that the asynchronous regime only yields realistic subthreshold variability (voltage variance [~=]4-9mV2) when driven by a restricted number of large synapses, compatible with strong thalamic drive. By contrast, we find that achieving realistic subthreshold variability with dense cortico-cortical inputs requires including weak but nonzero input synchrony, consistent with measured pairwise spiking correlations. We also show that without synchrony, the neural variability averages out to zero for all scaling limits with vanishing synaptic weights, independent of any balanced state hypothesis. This result challenges the theoretical basis for mean-field theories of the asynchronous state.

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Mammals achieve common neural coverage of visual scenes using distinct sampling behaviors

Most vertebrates use head and eye movements to quickly change gaze orientation and sample different portions of the environment with periods of stable fixation. Visual information must be integrated across several fixations to construct a more complete perspective of the visual environment. In concert with this sampling strategy, neurons adapt to unchanging input to conserve energy and ensure that only novel information from each fixation is processed. We demonstrate how adaptation recovery times and saccade properties interact, and thus shape spatiotemporal tradeoffs observed in the motor and visual systems of different species. These tradeoffs predict that in order to achieve similar visual coverage over time, animals with smaller receptive field sizes require faster saccade rates. Indeed, we find comparable sampling of the visual environment by neuronal populations across mammals when integrating measurements of saccadic behavior with receptive field sizes and V1 neuronal density. We propose that these mammals share a common statistically driven strategy of maintaining coverage of their visual environment over time calibrated to their respective visual system characteristics.

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Ocular following eye movements in marmosets follow complex motion trajectories

Ocular following eye movements help stabilize images on the retina and offer a window to study motion interpretation by visual circuits. We use these ocular following eye movements to study motion integration behavior in the marmosets. We characterize ocular following responses in the marmosets using different moving stimuli such as dot patterns, gratings, and plaids. The marmosets can accurately track motion along different directions and exhibit spatial frequency and speed sensitivity that closely matches the sensitivity reported in neurons from their motion selective area MT. Marmosets are also able to track the integrated motion of plaids, with tracking direction consistent with intersection of constraints model of motion integration. Marmoset ocular following responses are similar to responses in macaques and humans with certain species-specific differences in peak sensitivities. Such motion sensitive eye movement behavior in combination with direct access to cortical circuitry makes the marmoset model well suited to study the neural basis of motion integration. Significance statementOcular following is a reflexive eye tracking behavior in response to large visual field motion. It reflects the properties of underlying motion sensing circuits. One of the primary motion sensing areas in primates is area MT. In the primate species of marmosets, this and other cortical areas are easily accessible due to their lissencephalic brain. We demonstrate ocular following behavior in the marmosets for simple and complex motion trajectories and describe its characteristics. We then use ocular following to distinguish between different motion integration models. Our results show the utility of ocular following to study the neural basis for motion sensing in marmosets.

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Primate neocortex performs balanced sensory amplification

Sensory cortex amplifies relevant features of external stimuli. This sensitivity and selectivity arise through the transformation of inputs by cortical circuitry. We characterize the circuit mechanisms and dynamics of cortical amplification by making large-scale simultaneous measurements of single cells in awake primates and by testing computational models. By comparing network activity in both driven and spontaneous states with models, we identify the circuit as operating in a regime of balanced amplification. Incoming inputs are strongly but transiently amplified by recurrent excitation. Inhibition acts to counterbalance this excitation by rapidly quenching responses, thereby permitting tracking of time-varying stimuli. One-Sentence SummarySensory cortex uses balanced excitatory and inhibitory circuitry to boost weak signals while maintaining fast sensory dynamics in a changing environment.

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Feedforward mechanisms of masking in mouse V1

Sensory neurons not only encode stimuli that align with their receptive fields but are also modulated by context. For example, the responses of neurons in mouse primary visual cortex (V1) to gratings of their preferred orientation are modulated by the presence of superimposed orthogonal gratings ("plaids"). The effects of this modulation can be diverse: some neurons exhibit cross-orientation suppression while other neurons have larger responses to a plaid than its components. We investigated whether these diverse forms of masking could be explained by a unified circuit mechanism. We report that the suppression of cortical activity does not alter the effects of masking, ruling out cortical mechanisms. Instead, we demonstrate that the heterogeneity of plaid responses is explained by an interaction between stimulus geometry and orientation tuning. Highly selective neurons uniformly exhibit cross-orientation suppression, whereas in weakly-selective neurons masking depends on the spatial configuration of the stimulus, with effects transitioning systematically between suppression and facilitation. Thus, the diverse responses of mouse V1 neurons emerge as a consequence of the spatial structure of the afferent input to V1, with no need to invoke cortical interactions.

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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.

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Emergent orientation selectivity from random networks in mouse visual cortex

We study the connectivity principles underlying the emergence of orientation selectivity in primary visual cortex (V1) of mammals lacking an orientation map. We present a computational model in which random connectivity gives rise to orientation selectivity that matches experimental observations. It predicts that mouse V1 neurons should exhibit intricate receptive fields in the two-dimensional frequency domain, causing shift in orientation preferences with spatial frequency. We find evidence for these features in mouse V1 using calcium imaging and intracellular whole cell recordings.

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