scholarly journals Traumatic brain injury to primary visual cortex produces long-lasting circuit dysfunction

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jan C. Frankowski ◽  
Andrzej T. Foik ◽  
Alexa Tierno ◽  
Jiana R. Machhor ◽  
David C. Lyon ◽  
...  

AbstractPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.

2019 ◽  
Author(s):  
Marie Tolkiehn ◽  
Simon R. Schultz

AbstractOrientation tuning in mouse primary visual cortex (V1) has long been reported to have a random or “salt-and-pepper” organisation, lacking the structure found in cats and primates. Laminar in-vivo multi-electrode array recordings here reveal previously elusive structure in the representation of visual patterns in the mouse visual cortex, with temporo-nasally drifting gratings eliciting consistently highest neuronal responses across cortical layers and columns, whilst upward moving gratings reliably evoked the lowest activities. We suggest this bias in direction selectivity to be behaviourally relevant as objects moving into the visual field from the side or behind may pose a predatory threat to the mouse whereas upward moving objects do not. We found furthermore that direction preference and selectivity was affected by stimulus spatial frequency, and that spatial and directional tuning curves showed high signal correlations decreasing with distance between recording sites. In addition, we show that despite this bias in direction selectivity, it is possible to decode stimulus identity and that spatiotemporal features achieve higher accuracy in the decoding task whereas spike count or population counts are sufficient to decode spatial frequencies implying different encoding strategies.Significance statementWe show that temporo-nasally drifting gratings (i.e. opposite the normal visual flow during forward movement) reliably elicit the highest neural activity in mouse primary visual cortex, whereas upward moving gratings reliably evoke the lowest responses. This encoding may be highly behaviourally relevant, as objects approaching from the periphery may pose a threat (e.g. predators), whereas upward moving objects do not. This is a result at odds with the belief that mouse primary visual cortex is randomly organised. Further to this biased representation, we show that direction tuning depends on the underlying spatial frequency and that tuning preference is spatially correlated both across layers and columns and decreases with cortical distance, providing evidence for structural organisation in mouse primary visual cortex.


2019 ◽  
Vol 121 (6) ◽  
pp. 2202-2214 ◽  
Author(s):  
John P. McClure ◽  
Pierre-Olivier Polack

Multimodal sensory integration facilitates the generation of a unified and coherent perception of the environment. It is now well established that unimodal sensory perceptions, such as vision, are improved in multisensory contexts. Whereas multimodal integration is primarily performed by dedicated multisensory brain regions such as the association cortices or the superior colliculus, recent studies have shown that multisensory interactions also occur in primary sensory cortices. In particular, sounds were shown to modulate the responses of neurons located in layers 2/3 (L2/3) of the mouse primary visual cortex (V1). Yet, the net effect of sound modulation at the V1 population level remained unclear. In the present study, we performed two-photon calcium imaging in awake mice to compare the representation of the orientation and the direction of drifting gratings by V1 L2/3 neurons in unimodal (visual only) or multimodal (audiovisual) conditions. We found that sound modulation depended on the tuning properties (orientation and direction selectivity) and response amplitudes of V1 L2/3 neurons. Sounds potentiated the responses of neurons that were highly tuned to the cue’s orientation and direction but weakly active in the unimodal context, following the principle of inverse effectiveness of multimodal integration. Moreover, sound suppressed the responses of neurons untuned for the orientation and/or the direction of the visual cue. Altogether, sound modulation improved the representation of the orientation and direction of the visual stimulus in V1 L2/3. Namely, visual stimuli presented with auditory stimuli recruited a neuronal population better tuned to the visual stimulus orientation and direction than when presented alone. NEW & NOTEWORTHY The primary visual cortex (V1) receives direct inputs from the primary auditory cortex. Yet, the impact of sounds on visual processing in V1 remains controverted. We show that the modulation by pure tones of V1 visual responses depends on the orientation selectivity, direction selectivity, and response amplitudes of V1 neurons. Hence, audiovisual stimuli recruit a population of V1 neurons better tuned to the orientation and direction of the visual stimulus than unimodal visual stimuli.


2021 ◽  
Author(s):  
Marton Albert Hajnal ◽  
Duy Tran ◽  
Michael Einstein ◽  
Mauricio Vallejo Martelo ◽  
Karen Safaryan ◽  
...  

Primary visual cortex (V1) neurons integrate motor and multisensory information with visual inputs during sensory processing. However, whether V1 neurons also integrate and encode higher-order cognitive variables is less understood. We trained mice to perform a context-dependent cross-modal decision task where the interpretation of identical audio-visual stimuli depends on task context. We performed silicon probe population recordings of neuronal activity in V1 during task performance and showed that task context (whether the animal should base its decision on visual or auditory stimuli) can be decoded during both intertrial intervals and stimulus presentations. Context and visual stimuli were represented in overlapping populations but were orthogonal in the population activity space. Context representation was not static but displayed distinctive dynamics upon stimulus onset and offset. Thus, activity patterns in V1 independently represent visual stimuli and cognitive variables relevant to task execution.


2017 ◽  
Vol 29 (1) ◽  
pp. 54-69 ◽  
Author(s):  
Chunhai Chen ◽  
Xiaoling Zhong ◽  
Derek K Smith ◽  
Wenjiao Tai ◽  
Jianjing Yang ◽  
...  

Abstract Injury to the adult brain induces activation of local astrocytes, which serves as a compensatory response that modulates tissue damage and recovery. However, the mechanism governing astrocyte activation during brain injury remains largely unknown. Here we provide in vivo evidence that SOX2, a transcription factor critical for stem cells and brain development, is also required for injury-induced activation of adult cortical astrocytes. Genome-wide chromatin immunoprecipitation-seq analysis of mouse cortical tissues reveals that SOX2 binds to regulatory regions of genes associated with signaling pathways that control glial cell activation, such as Nr2e1, Mmd2, Wnt7a, and Akt2. Astrocyte-specific deletion of Sox2 in adult mice greatly diminishes glial response to controlled cortical impact injury and, most unexpectedly, dampens injury-induced cortical loss and benefits behavioral recovery of mice after injury. Together, these results uncover an essential role of SOX2 in somatic cells under pathological conditions and indicate that SOX2-dependent astrocyte activation could be targeted for functional recovery after traumatic brain injury.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mineki Oguchi ◽  
Jiang Jiasen ◽  
Toshihide W. Yoshioka ◽  
Yasuhiro R. Tanaka ◽  
Kenichi Inoue ◽  
...  

AbstractIn vivo calcium imaging with genetically encoded indicators has recently been applied to macaque brains to monitor neural activities from a large population of cells simultaneously. Microendoscopic calcium imaging combined with implantable gradient index lenses captures neural activities from deep brain areas with a compact and convenient setup; however, this has been limited to rodents and marmosets. Here, we developed miniature fluorescent microscopy to image neural activities from the primary visual cortex of behaving macaques. We found tens of clear fluorescent signals from three of the six brain hemispheres. A subset of these neurons showed clear retinotopy and orientation tuning. Moreover, we successfully decoded the stimulus orientation and tracked the cells across days. These results indicate that microendoscopic calcium imaging is feasible and reasonable for investigating neural circuits in the macaque brain by monitoring fluorescent signals from a large number of neurons.


2020 ◽  
Author(s):  
Jan C. Frankowski ◽  
Andrzej T. Foik ◽  
Jiana R. Machhor ◽  
David C. Lyon ◽  
Robert F. Hunt

SummaryPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effect of traumatic brain injury on visual system function. Here we applied a mild focal contusion injury to primary visual cortex (V1) in adult mice. We found that, although V1 was largely intact in brain-injured mice, there was a reduction in the number of inhibitory interneurons that extended into deep cortical layers. In general, we found a preferential reduction of interneurons located in superficial layers, near the impact site, while interneurons positioned in deeper layers were better preserved. Three months after injury, V1 neurons showed dramatically reduced responses to visual stimuli and weaker orientation selectivity and tuning, consistent with the loss of cortical inhibition. Our results demonstrate that V1 neurons no longer robustly and stably encode visual input following a mild traumatic injury.HighlightsInhibitory neurons are lost throughout brain injured visual cortexVisually-evoked potentials are severely degraded after injuryInjured V1 neurons show weaker selectivity and tuning consistent with reduced interneurons


2018 ◽  
Author(s):  
Anton Arkhipov ◽  
Nathan W. Gouwens ◽  
Yazan N. Billeh ◽  
Sergey Gratiy ◽  
Ramakrishnan Iyer ◽  
...  

ABSTRACTDespite advances in experimental techniques and accumulation of large datasets concerning the composition and properties of the cortex, quantitative modeling of cortical circuits under in-vivo-like conditions remains challenging. Here we report and publicly release a biophysically detailed circuit model of layer 4 in the mouse primary visual cortex, receiving thalamo-cortical visual inputs. The 45,000-neuron model was subjected to a battery of visual stimuli, and results were compared to published work and new in vivo experiments. Simulations reproduced a variety of observations, including effects of optogenetic perturbations. Critical to the agreement between responses in silico and in vivo were the rules of functional synaptic connectivity between neurons. Interestingly, after extreme simplification the model still performed satisfactorily on many measurements, although quantitative agreement with experiments suffered. These results emphasize the importance of functional rules of cortical wiring and enable a next generation of data-driven models of in vivo neural activity and computations.AUTHOR SUMMARYHow can we capture the incredible complexity of brain circuits in quantitative models, and what can such models teach us about mechanisms underlying brain activity? To answer these questions, we set out to build extensive, bio-realistic models of brain circuitry employing systematic datasets on brain structure and function. Here we report the first modeling results of this project, focusing on the layer 4 of the primary visual cortex (V1) of the mouse. Our simulations reproduced a variety of experimental observations in a large battery of visual stimuli. The results elucidated circuit mechanisms determining patters of neuronal activity in layer 4 – in particular, the roles of feedforward thalamic inputs and specific patterns of intracortical connectivity in producing tuning of neuronal responses to the orientation of motion. Simplification of neuronal models led to specific deficiencies in reproducing experimental data, giving insights into how biological details contribute to various aspects of brain activity. To enable future development of more sophisticated models, we make the software code, the model, and simulation results publicly available.


2021 ◽  
Author(s):  
Dylan Barbera ◽  
Nicholas J. Priebe ◽  
Lindsey L. Glickfeld

AbstractSensory 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.


2016 ◽  
Author(s):  
Ovidiu Jurjut ◽  
Petya Georgieva ◽  
Laura Busse ◽  
Steffen Katzner

AbstractA fundamental property of visual cortex is to enhance the representation of those stimuli that are relevant for behavior, but it remains poorly understood how such enhanced representations arise during learning. Using classical conditioning in mice, we show that orientation discrimination is learned in a sequence of distinct behavioral stages, in which animals first rely on stimulus appearance before exploiting its orientation to guide behavior. After confirming that orientation discrimination under classical conditioning requires primary visual cortex (V1), we measured, during learning, response properties of V1 neurons. Learning improved neural discriminability, sharpened orientation tuning and led to higher contrast sensitivity. Remarkably, these learning-related improvements in the V1 representation were fully expressed before successful orientation discrimination was evident in the animals’ behavior. We propose that V1 plays a key role early in discrimination learning to enhance behaviorally relevant sensory information.


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