Biology subjects

Joesch, M.

Publications and source records attributed to Joesch, M..

8 recordsLinked to original sources

bioRxiv2026

Intrinsic Population Dynamics are a Neuronal Substrate for Visual Attention

Perception results from a dynamic interplay between the feedforward processing of sensory stimuli and intrinsic neural activity 1, which is often dismissed as noise 2. To tailor perceptual processes to the organisms current needs on a continuous, moment-to-moment basis, intrinsic dynamics - rather than just being noise - have been suggested to reflect prior expectations 3,4, task demands 5, and attentional focus 6. Here, we identify a novel signature of attentive state in which intrinsic, collective neural activity modulates visuospatial attention by dynamically interacting with sensory input within the superior colliculus (SC), a midbrain hub that integrates bottom-up visual input with top-down signals 7. We show that these intrinsic dynamics organize cell activity into structured, blob-like features that are temporally and topographically localized and that rival sensory-evoked responses in strength. These features emerge as animals learn to engage in the visual detection task, and predict behavioral outcomes on a trial-by-trial basis. Although independent of sensory input or overt behavior, the features can be recruited to enhance visual responses four-fold in the attentive state, generating a "dynamic saliency map" that aligns with reaction times and behavioral outcomes. A computational model indicates that tunable blob-like features can arise from local excitatory-inhibitory interactions within the SC, and enhance sensory-evoked responses in line with observations. Together, our results identify state-dependent intrinsic population activity that interacts with sensory input to give rise to a saliency-map-like representation linked to flexible, goal-directed behavior.

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bioRxiv2026

The functional organization of retinal input to the mouse superior colliculus

The superior colliculus integrates retinal input to drive rapid, adaptive visual behavior, yet how the functional diversity of retinal ganglion cell types is represented in superior colliculus remains poorly understood. Using chronic two-photon calcium imaging of retinal ganglion cell axonal boutons in awake mice, we recorded over 200,000 boutons across superficial superior colliculus layers -- a scale that enabled systematic comparison with large-scale ex vivo retinal datasets. This revealed that the superior colliculus receives a near-complete sampling of retinal ganglion cell functional diversity. Functionally distinct response types were organized in systematic laminar gradients: not only response properties such as direction selectivity and contrast suppression, but retinal response types themselves varied systematically with depth. To probe how this organized input encodes natural scenes, we trained a "digital twin" deep network model on natural movie responses and validated its generalization to parametric stimuli, including cell type identification. Leveraging this model to generate predicted responses to looming stimuli, we identify a discrete subset of retinal response types tuned for collision detection at low angular thresholds -- a specialization embedded within a broader, non-specialized retinal population. The digital twin is made publicly available as a community resource. Together, these findings provide a comprehensive functional map of retinal drive to the superior colliculus and an in silico platform for linking retinal cell types to behaviorally relevant superior colliculus computations.

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bioRxiv2023

A thalamic hub of action cues coordinates early visual processing and perception

Distinguishing between sensory experiences elicited by external stimuli and an animals own actions is critical for accurate perception and motor control. However, the diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action cue hub that coordinates both visual processing in the brains first visual relay and motor commands. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge (CD) center, integrating visual translational optic flow signals and motor copies from saccades, locomotion, and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and refine perception, as shown for the superior colliculus and a depth estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended CD architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network enabling visual perception during action.

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bioRxiv2023

Gap junctions arbitrate binocular course control in flies

Animals utilize visual motion cues to maintain stability and navigate accurately. The optomotor response, a reflexive behavior for visual stabilization, has been used to study this visuomotor transformation. However, there is a disparity between the simplicity of this behavior and the intricate circuit components believed to govern it. Here we bridge this divide by exploring the course control repertoire in Drosophila and establishing a direct link between behavior and the underlying circuit motifs. Specifically, we demonstrate that visual motion information from both eyes plays a crucial role in movement control through bilateral interactions facilitated by gap junctions. These electrical interactions augment the classic stabilization behavior by inverting the response direction and the behavioral strategy. Our findings reveal how animals combine monocular motion cues to generate a variety of behaviors, determine the functional role of the circuit components, and show that gap junctions can mediate non-linear operations with a decisive role in animal behavior.

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bioRxiv2022

Subcortical circuit dysfunctions delay perceptual decision-making in autism models

Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in three independent models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments - a non-perceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1) mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment, and define a non-developmental source of such deficits in ASD.

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bioRxiv2022

Panoramic visual statistics shape retina-wide organization of receptive fields

Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types.

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bioRxiv2021

An extended toolkit for production and use of RVdG-CVS-N2c rabies viral vectors uncovers hidden hippocampal connections

To understand the function of neuronal circuits it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low-throughput, low-selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotrophic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of "starter" AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.

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bioRxiv2019

Novelty gates memory formation through ventro-dorsal hippocampal interaction

Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty.

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