Adrian J. Duszkiewicz (Paul Dudchenko's Lab)

Division of Psychology, University of Stirling, UK

We use Cambridge Neurotech probes to record large neuronal populations in the rodent head-direction circuit - the brain’s internal compass. Focusing on the postsubiculum, a cortical area with exceptionally sharp directional tuning, we leverage this low-dimensional and highly tractable neural signal to study cortical function and dysfunction in rat models of neurodevelopmental disorders.

Current Publications:
https://www.nature.com/articles/s41593-024-01588-5
https://www.cell.com/trends/neurosciences/abstract/S0166-2236(25)00190-0

Autism spectrum disorder often involves atypical sensory processing, including hypersensitivity and difficulties with combining information across sensory streams. Fragile X Syndrome (FXS), caused by mutations in the FMR1 gene, is a common inherited form of autism. Although rodent models have advanced our grasp of neural mechanisms underlying sensory hypersensitivity in FXS, the circuit-level origins of impaired multisensory integration remain largely unexplored. Here, we provide the first evidence that ablation of the FMR1 gene disrupts sensory integration in the cortical circuits underlying spatial orientation. Spatial orientation in mammals depends on the ability to integrate information across sensory modalities. Central to this process are head-direction (HD) cells, each tuned to a specific heading direction of the animal, together creating an internal compass. This compass is updated by vestibular signals that encode angular head velocity (AHV) and is anchored to the external world via visual input. Taking advantage of the HD system’s experimental accessibility, we examined how these two information streams interact in Fmr1^-/y rats, a model of FXS. To that end, we simultaneously recorded populations of neurons from postsubiculum (PoSub; 30-115 cells/session) and retrosplenial cortex (RSC; 52-171 cells/session) using silicon probes in adult Fmr1^-/y (n = 7) and wild-type (WT, n = 8) rats. During a visual-vestibular mismatch task, rats explored an elevated platform while a prominent visual landmark was displayed on a portion of the 360° LED screen surrounding the arena. When this landmark was rotated by 45° or 90°, HD neurons in WT rats shifted their preferred firing directions only partway, consistent with integration of visual and self-motion inputs. In contrast, HD cells in Fmr1^-/y rats rotated exactly with the visual landmark, indicating a lack of vestibular contribution to reorientation. This was further reflected in reduced AHV tuning across both brain regions and greater instability of the HD signal in darkness. Finally, to establish whether this disruption of sensory integration is specific to the FXS rat model, we tested the rat model of SYNGAP1-related intellectual disability (Syngap1^-/+ rats) on the same experimental protocol, and found that Syngap1^-/+ rats (n = 6, n = 5 WT littermates), in contrast to Fmr1^-/y rats, exhibit intact sensory integration and AHV tuning in the HD system. Further experiments will determine whether disrupted sensory integration and AHV tuning in Fmr1^-/y rats translates to impairments in behavioural tasks that critically rely on self-motion signals.