Biology subjects

Farrow, K.

Publications and source records attributed to Farrow, K..

12 recordsLinked to original sources

bioRxiv2026

Cooperative processing of visual threat across collicular pathways

Rapid defensive actions require the transformation of sensory cues into appropriate motor responses. The superior colliculus is central to this transformation, containing defined cell-types that form parallel output pathways linking visual inputs to distinct behaviors. However, whether these pathways act independently or cooperate remains unclear. Here we combine cell-type-specific inhibition, large-scale electrophysiology, and functional ultrasound imaging to determine how these pathways contribute to visually evoked defensive behaviors. Inhibiting either narrow-field or wide-field neurons impaired escape to overhead visual threats, demonstrating that both pathways contribute to escape. Recordings from downstream targets revealed a compact representation in the deeper layers of the superior colliculus that selectively distinguished visual stimuli associated with escape, whereas the lateral posterior thalamus contained a broader representation of visual stimuli. The representation of visual threat in the deeper layers of the superior colliculus predicted escape initiation and vigor in freely moving animals. Across the brain, functional ultrasound imaging showed that visual stimuli recruited distinct patterns of activity that could not be explained by response magnitude alone or by the contribution of single cell-types. Together, these results reveal a cooperative circuit architecture in which parallel pathways carry distinct but complementary signals that jointly support visually evoked escape.

neuroscience↗

bioRxiv2026

Visual field position shapes input sampling and output routing in the superior colliculus

Animals use the location of visual stimuli to select appropriate actions1-5, and the upper and lower visual field often carry different ecological and behavioral meaning6-9. In mice, the superior colliculus is a key central hub that transforms visual input into orienting, defensive, and approach behaviors3,10-13. Its superficial layers receive retinotopically organized input from the retina and contain genetically defined cell types with distinct downstream projections, including wide-field neurons that project to the lateral posterior thalamus and narrow-field neurons that target the parabigeminal nucleus and deeper collicular layers14-18. These features raise the question of whether circuits of the superior colliculus are repeated across visual space or exhibit visual-field-dependent specializations. Here, we show that the mouse superficial superior colliculus contains visual-field-dependent circuit modules. Dual-color rabies tracing revealed that wide-field and narrow-field neurons receive input from a largely shared set of brain regions, whereas upper- and lower-field domains differ in how they sample those inputs. Some source regions preferentially innervate one visual-field domain, producing biased regional input strength, while others contain topographically segregated projecting neurons that target upper- or lower-field domains. MAPseq showed that most superficial collicular neurons project to single downstream targets, with upper- and lower-field populations differing in target probability. Two-photon calcium imaging further showed that wide-field neurons in upper- and lower-field domains differ in stimulus selectivity. Together, these findings reveal a visual-field-dependent wiring logic that biases how the superior colliculus samples inputs and routes signals to downstream pathways. HighlightsO_LIWide- and narrow-field neurons receive broadly overlapping inputs C_LIO_LIUpper- and lower-field domains differ in input strength and topographic organization C_LIO_LIMost superficial collicular neurons project to a single target C_LIO_LIVisual field position biases downstream target probability C_LI

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bioRxiv2025

Ambient Light Impacts Innate Behaviors of New-World and Old-World Mice

Animals encounter predators and prey under diverse lighting conditions that signal different risks and opportunities1-4, yet how ambient illumination shapes innate approach and avoidance behaviors remains poorly understood. Here we have systematically tested the visually guided behaviors of New-World (North American Peromyscus) and Old-World (Eurasian Mus) mice under conditions mimicking bright daylight or dim moonlit environments. We identified common and species-specific adaptations to the different lighting conditions. Across species, dim light enhanced the speed and vigor of escape responses to predator-like looming stimuli. However, species diverged in their reactions to non-threatening stimuli, with Mus musculus and Peromyscus polionotus increasing aversive behaviors under dim light, while Peromyscus maniculatus showed stronger avoidance under bright conditions. Finally, although ambient light levels had a common effect on exploratory behavior, these changes were not predictive of subsequent visually evoked behaviors. Our findings reveal that ambient lighting profoundly and differentially shapes innate behavioral strategies across species, and demonstrate that these context-specific survival responses are inherited rather than learned.

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bioRxiv2025

Dendritic Architecture Enables de Novo Computation of Salient Motion in the Superior Colliculus

Dendritic architecture plays a crucial role in shaping how neurons extract behaviorally relevant information from sensory inputs. Wide-field neurons in the superior colliculus integrate visual information from the retina to encode cues critical for visually guided orienting behaviors. However, the principles governing how these neurons filter their inputs to generate appropriate responses remain unclear. Using viral tracing, two-photon calcium imaging, and computational modeling, we show that wide-field neurons receive functionally diverse inputs from twelve retinal ganglion cell types, forming a layered, type-specific organization along their dendrites. This structured arrangement allows wide-field neurons to multiplex salient motion cues, selectively amplifying movement and suppressing static features. Computational models reveal that the spatial organization of dendrites and inputs enables the selective extraction of behaviorally relevant stimuli, including de novo computations. Our findings underscore the critical role of dendritic architecture in shaping sensory processing and neural circuit function.

neuroscience↗

bioRxiv2025

Predicting the Regenerative Potential of Retinal Ganglion Cells Based on Developmental Growth Trajectories

Retinal ganglion cells in the mammalian central nervous system fail to regenerate following injury, with the capacity to survive and regrow varying by cell type. This variability may be linked to differences in developmental programs that overlap with the genetic pathways that mediate regeneration. To explore this correlation, we compared the structural changes in mouse retinal ganglion cells during development with those occurring after axonal injury. The dendritic trees of over 1,000 ganglion cells were reconstructed at different developmental stages, revealing that each cell type follows a distinct timeline. ON-sustained (sON) cells reach maturity by P14, whereas ON-transient (tON) cells achieve their maximum dendritic size by P10. Modeling of the dendritic changes indicate that while sON and tON follow similar growth programs the onset of growth was later in sON. After optic nerve crush, the remodeling of dendritic architecture differed between the two cell-types. sON cells exhibited rapid dendritic shrinkage, while tON cells shrank more gradually with changes in branching features. Following injury, sON cells reverted to an earlier developmental state than tON cells. In addition, after co-deletion of PTEN and SOC3, neurons appeared to regress further back in developmental time. Our results provide evidence that a ganglion cells resilience to injury and regenerative potential is predicted by its maturation timeline. Understanding these intrinsic differences could inform targeted neuroprotective interventions.

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bioRxiv2024

Local glycolysis supports injury-induced axonal regeneration

Successful axonal regeneration following injury requires the effective allocation of energy. Mitochondria play a pivotal role, accumulating at the tips of growing axons to fuel regeneration. However, how axons withstand the initial disruption in mitochondrial energy production caused by the injury, and subsequently initiate regrowth is poorly understood. Using retinal cultures in a multicompartment microfluidic device, we observed increased regrowth and enhanced mitochondrial trafficking in the axons of retinal ganglion cells with the deletion of both Pten and Socs3. While wild-type axons relied on mitochondrial metabolism, after injury, in the absence of Pten and Socs3, energy production was demonstrated to be supported by local glycolysis. Slowing down glycolysis in these axons impaired both regrowth and energy production. Together, these observations reveal that glycolytic ATP, combined with sustained mitochondrial transport, is essential for injury-induced axonal regrowth, providing new insights into the metabolic underpinnings of axonal regeneration.

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bioRxiv2023

Retinal origin of orientation but not direction selective maps in the superior colliculus

Neurons in the mouse superior colliculus ("colliculus") are arranged in ordered spatial maps. While orientationselective (OS) neurons form a concentric map aligned to the center of vision, direction-selective (DS) neurons are arranged in patches with changing preferences across the visual field. It remains unclear if these maps are a consequence of feed-forward input from the retina or local computations in the colliculus. To determine whether these maps originate in the retina, we mapped the local and global distribution of orientation- and direction-selective retinal ganglion cell boutons using in-vivo two-photon calcium imaging. We found that OS boutons formed patches that matched the distribution of OS neurons within the colliculus. DS boutons displayed less regional specializations, better reflecting the organization of DS neurons in the retina. Both eyes convey similar orientation but different DS inputs to the colliculus, as shown in recordings from retinal explants. These data demonstrate that orientation and direction maps within the colliculus are independent, implying that orientation maps are inherited from the retina, but direction maps require local circuits.

neuroscience↗

bioRxiv2023

The neural basis of defensive behaviour evolution in Peromyscus mice

Evading imminent predator threat is critical for survival. Effective defensive strategies can vary, even between closely related species. However, the neural basis of such species-specific behaviours is still poorly understood. Here we find that two sister species of deer mice (genus Peromyscus) show different responses to the same looming stimulus: P. maniculatus, which occupy densely vegetated habitats, predominantly dart to escape, while the open field specialist, P. polionotus, pause their movement. This difference arises from species-specific escape thresholds, is largely context-independent, and can be triggered by both visual and auditory threat stimuli. Using immunohistochemistry and electrophysiological recordings, we find that although visual threat activates the superior colliculus in both species, the role of the dorsal periaqueductal gray (dPAG) in driving behaviour differs. While dPAG activity scales with running speed and involves both excitatory and inhibitory neurons in P. maniculatus, the dPAG is largely silent in P. polionotus, even when darting is triggered. Moreover, optogenetic activation of excitatory dPAG neurons reliably elicits darting behaviour in P. maniculatus but not P. polionotus. Together, we trace the evolution of species-specific escape thresholds to a central circuit node, downstream of peripheral sensory neurons, localizing an ecologically relevant behavioural difference to a specific region of the complex mammalian brain.

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bioRxiv2022

Pathway-specific inputs to the superior colliculus support flexible triggering of innate behaviors

Behavioral flexibility requires the ability to modify the feedforward transmission of sensory information. The superior colliculus mediates visually guided innate defensive behaviors via cell-type specific projections. However, how brain-wide inputs to the superior colliculus are organized to modulate visual processing and enable flexible behavior remains unknown. To determine these rules, we focused on inhibitory projection (Gad2) neurons. Trans-synaptic tracing and neuronal recordings revealed that Gad2 neurons projecting to the dorsal lateral geniculate nucleus (LGd) and the parabigeminal nucleus (PBG) form two separate anatomical and functional populations, where each circuit received a different set of non-retinal inputs. Inhibiting LGd or PBG projecting Gad2 neurons resulted in opposing effects on behavior; increasing freezing or escape probability to visual looming stimuli, respectively. These data suggest that projection-specific sampling of brain-wide inputs provide a circuit design principle that enables feed-forward transfer of visual threat to be independently adjusted to produce context specific behavior.

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bioRxiv2020

Brain-wide mapping of neural activity mediating collicular-dependent behaviors

Neuronal cell-types are arranged in brain-wide circuits to guide behavior. In mice, the superior colliculus is comprised of a set of cell-types that each innervate distinct downstream targets. Here we reveal the brain-wide networks downstream of four collicular cell-types by combining functional ultrasound imaging (fUSi) with optogenetics to monitor neural activity at a resolution of ~100 m. Each neuronal group triggered different behaviors, and activated distinct, partially overlapping sets of brain nuclei. This included regions not previously thought to mediate defensive behaviors, e.g. the posterior paralaminar nuclei of the thalamus (PPnT), that we show to play a role in suppressing habituation. Electrophysiological recordings support the fUSi findings and show that neurons in the downstream nuclei preferentially respond to innately threatening visual stimuli. This work provides insight into the functional organization of the networks governing defensive behaviors and demonstrates an experimental approach to explore the whole-brain neuronal activity downstream of targeted cell-types.

neuroscience↗

bioRxiv2020

Reconsidering the border between the visual and posterior parietal cortex of mice

The posterior parietal cortex (PPC) contributes to multisensory and sensory-motor integration, as well as spatial navigation. Based on studies in primates, the PPC is composed of several subdivisions with differing connection patterns, including areas that exhibit retinotopy. In mice the exact anatomical location and composition of the PPC is poorly understood. We present a revised delineation in which we classify the higher-order visual areas RL, AM and MMA as subregions of the mouse PPC. Retrograde and anterograde tracing revealed connectivity, characteristic for primate PPC, with sensory, retrosplenial, orbitofrontal, cingulate and motor cortex, as well as with several thalamic nuclei and the superior colliculus in the mouse. Regarding cortical input, RL receives major input from the somatosensory barrel field, while AM receives more input from the trunk, whereas MMA receives strong inputs from retrosplenial, cingulate and orbitofrontal cortices. These input differences suggest that each new PPC sub-region has a distinct function. Summarized, we put forward a new refined cortical map, including a mouse PPC that contains at least 6 sub-regions, RL, AM, MMA and PtP, MPta, LPta/A. These results will facilitate a more detailed understanding about the role that the PPC and its subdivisions play in multisensory integration-based behavior in mice. HighlightsO_LIHigher-order visual areas RL, AM and MMA are part of the posterior parietal cortex (PPC) of the mouse based on connectivity. C_LIO_LIThe mouse PPC contains at least 6 sub-regions, including RL, AM, MMA, PtP, LPtA/A and MPtA C_LIO_LISpecialized cortical input patterns to the new PPC subdivisions may reflect division of function. C_LIO_LIA new flattened map for mouse cortex represents refined auditory, visual, retrosplenial and PPC areas. C_LI

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bioRxiv2018

Target specific routing of visual information by the superior colliculus

Using sensory information to trigger different behaviours relies on circuits that pass-through brain regions. However, the rules by which parallel inputs are routed to different downstream targets is poorly understood. The superior colliculus mediates a set of innate behaviours, receiving input from ~30 retinal ganglion cell types and projecting to behaviourally important targets including the pulvinar and parabigeminal nucleus. Combining transsynaptic circuit tracing with in-vivo and ex-vivo electrophysiological recordings we observed a projection specific logic where each collicular output pathway sampled a distinct set of retinal inputs. Neurons projecting to the pulvinar or parabigeminal nucleus uniquely sampled 4 and 7 cell types, respectively. Four others innervated both pathways. The visual response properties of retinal ganglion cells correlated well with those of their disynaptic targets. These findings suggest that projection specific sampling of retinal inputs forms a mechanistic basis for the selective triggering of visually guided behaviours by the superior colliculus.

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