Biology subjects

Kremkow, J.

Publications and source records attributed to Kremkow, J..

6 recordsLinked to original sources

bioRxiv2022

Retinal waves align the concentric orientation map in mouse superior colliculus to the center of vision

Neurons in the mouse superior colliculus (SC) are arranged in an orientation preference map that has a concentric organization, which is aligned to the center of vision and the optic flow experienced by the mouse. The developmental mechanisms that underlie this functional map remain unclear. Here, we propose that the spatiotemporal properties of spontaneous retinal waves during development provide a scaffold to establish the concentric orientation map in the mouse SC and its alignment to the optic flow. We test this hypothesis by modelling the orientation-tuned SC neurons that receive ON/OFF retinal inputs. Our results suggest that the stage III retinal wave properties, namely OFF delayed response and the wave propagation direction bias, are key factors that regulate the spatial organization of the SC orientation map. Specifically, the OFF delay mediates the establishment of orientation-tuned SC neurons by segregating their ON/OFF receptive subfields, the wave-like activities facilitate the formation of a concentric pattern, and the wave direction biases align the orientation map to the center of vision. Taken together, our model suggests that retinal waves may play an instructive role in establishing functional properties of SC neurons and provides a promising mechanism for explaining the correlations between the optic flow and the SC orientation map.

neuroscience↗

bioRxiv2022

Absence of the fragile X mental retardation protein alters response patterns to sounds in the auditory midbrain

Among the different autism spectrum disorders, Fragile X Syndrome (FXS) is the most common inherited cause of mental retardation. Sensory and especially auditory hypersensitivity is a key symptom in patients, which is well mimicked in the Fmr1 -/- mouse model. However, the physiological mechanisms underlying FXSs acoustic hypersensitivity in particular remain poorly understood. Here, we categorized spike response patterns to pure tones of different frequencies and intensities from neurons in the Inferior Colliculus (IC), a central integrator in the ascending auditory pathway. Based on this categorization we analyzed differences in response patterns between IC neurons of WT and Fmr1 -/- mice. Our results report broadening of frequency tuning, an increased firing in response to monaural as well as binaural stimuli, an altered balance of excitation-inhibition, and reduced response latencies, all expected features of acoustic hypersensitivity. Furthermore, we were surprised to notice that all neuron response types in Fmr1 -/- mice displayed enhanced offset-rebound activity outside their excitatory frequency response area. These results provide evidence that the loss of Fmr1 not only increases spike responses in IC neurons similar to auditory brainstem neurons, but also changes response patterns such as offset spiking. One can speculate this to be an underlying aspect of the receptive language problems associated with Fragile X syndrome.

neuroscience↗

bioRxiv2022

A theory of cortical map formation in the visual brain

The cerebral cortex receives multiple afferents from the thalamus that segregate by stimulus modality forming cortical maps for each sense. In vision, the primary visual cortex maps the multiple dimensions of the visual stimulus in patterns that vary across species for reasons unknown. Here we introduce a general theory of cortical map formation, which proposes that map diversity emerges from species variations in the thalamic afferent density sampling sensory space. In the theory, increasing afferent sampling density enlarges the cortical domains representing the same visual point, allowing the segregation of afferents and cortical targets by multiple stimulus dimensions. We illustrate the theory with an afferent-density model that accurately replicates the maps of different species through afferent segregation followed by thalamocortical convergence pruned by visual experience. Because thalamocortical pathways use similar mechanisms for axon segregation and pruning, the theory may extend to other sensory areas of the mammalian brain.

neuroscience↗

bioRxiv2021

Strong and specific connections between retinal axon mosaics and midbrain neurons revealed by large scale paired recordings

The superior colliculus (SC) is a midbrain structure that plays important roles in visually guided behaviors. Neurons in the SC receive afferent inputs from retinal ganglion cells (RGC), the output cells of the retina, but how SC neurons integrate RGC activity in vivo is unknown. SC neurons might be driven by strong but sparse retinal inputs, thereby reliably transmitting specific retinal functional channels. Alternatively, SC neurons could sum numerous but weak inputs, thereby extracting new features by combining a diversity of retinal signals. Here, we discovered that high-density electrodes simultaneously capture the activity and the location of large populations of retinal axons and their postsynaptic SC target neurons, permitting us to investigate the retinocollicular circuit on a structural and functional level in vivo. We show that RGC axons in the mouse are organized in mosaics that provide a single cell precise representation of the retina as input to SC. This isomorphic mapping between retina and SC builds the scaffold for highly specific wiring in the retinocollicular circuit which we show is characterized by strong connections and limited functional convergence, established in log-normally distributed connection strength. Because our novel method of large-scale paired recordings is broadly applicable for investigating functional connectivity across brain regions, we were also able to identify retinal inputs to the avian optic tectum of the zebra finch. We found common wiring rules in mammals and birds that provide a precise and reliable representation of the visual world encoded in RGCs to neurons in retinorecipient areas. HIGHLIGHTSO_LIHigh-density electrodes capture the activity of afferent axons and target neurons in vivo C_LIO_LIRetinal ganglion cells axons are organized in mosaics C_LIO_LISingle cell precise isomorphism between dendritic and axonal RGC mosaics C_LIO_LIMidbrain neurons are driven by sparse but strong retinal inputs C_LIO_LIFunctional wiring of the retinotectal circuit is similar in mammals and birds C_LI

neuroscience↗

bioRxiv2021

Tangential high-density electrode insertions allow to simultaneously measure neuronal activity across an extended region of the visual field in mouse superior colliculus

The superior colliculus (SC) is a midbrain structure that plays a central role in visual processing. Although we have learned a considerable amount about the function of single SC neurons, the way in which sensory information is represented and processed on the population level in awake behaving animals and across a large region of the retinotopic map is still largely unknown. Partially because the SC is anatomically located below the cortical sheet and the transverse sinus, it is technically difficult to measure neuronal activity from a large population of neurons in SC. To address this, we propose a tangential recording configuration using high-density electrode probes (Neuropixels) in mouse SC in vivo that permits a large number of recording sites (~200) accessibility inside the SC circuitry. This approach thereby provides a unique opportunity to measure the activity of SC neuronal populations composing up to ~2 mm of SC tissue and characterized by receptive fields covering an extended region in the visual field. Here we describe how to perform tangential recordings along the anterior-posterior and the medio-lateral axis of the mouse SC in vivo and how to combine this approach with optogenetic tools for cell-type identification on the population level.

neuroscience↗

bioRxiv2021

Predicting behavior from eye movement and whisking asymmetry

Navigation through complex environments requires motor planning, motor preparation and the coordination between multiple sensory motor modalities. For example, the stepping motion when we walk is coordinated with motion of the torso, arms, head and eyes. In rodents, movement of the animal through the environment is often coordinated with whisking. Here we trained head fixed mice, navigating a floating Airtrack plus maze, to overcome their directional preference and use cues indicating the direction of movement expected in each trial. Once cued, mice had to move backward out of a lane, then turn in the correct direction, and enter a new lane. In this simple paradigm, as mice begin to move backward, they position their whiskers asymmetrically: whiskers on one side of the face protract, and on the other side they retract. This asymmetry reflected the turn direction. Additionally, on each trial, mice move their eyes conjugately in the direction of the upcoming turn. Not only do they move their eyes, but saccadic eye movement is coordinated with the asymmetric positioning of the whiskers. Our analysis shows that the asymmetric positioning of the whiskers predicts the direction of turn that mice will make at an earlier stage than eye movement does. We conclude that, when mice move or plan to move in complex real-world environments, their motor plan and behavioral state can be read out in the movement of both their whiskers and eyes.

neuroscience↗