Thesis_AP_final.pdf (6.45 MB)
CONTEXTUAL MODULATION OF NEURAL RESPONSES IN THE MOUSE VISUAL SYSTEM
thesisposted on 2021-05-07, 19:11 authored by Alexandr PakAlexandr Pak
The visual system is responsible for processing visual input, inferring its environmental causes, and assessing its behavioral significance that eventually relates to visual perception and guides animal behavior. There is emerging evidence that visual perception does not simply mirror the outside world but is heavily influenced by contextual information. Specifically, context might refer to the sensory, cognitive, and/or behavioral cues that help to assess the behavioral relevance of image features. One of the most famous examples of such behavior is visual or optical illusions. These illusions contain sensory cues that induce a subjective percept that is not aligned with the physical nature of the stimulation, which, in turn, suggests that a visual system is not a passive filter of the outside world but rather an active inference machine.
Such robust behavior of the visual system is achieved through intricate neural computations spanning several brain regions that allow dynamic visual processing. Despite the numerous attempts to gain insight into those computations, it has been challenging to decipher the circuit-level implementation of contextual processing due to technological limitations. These questions are of great importance not only for basic research purposes but also for gaining deeper insight into neurodevelopmental disorders that are characterized by altered sensory experiences. Recent advances in genetic engineering and neurotechnology made the mouse an attractive model to study the visual system and enabled other researchers and us to gain unprecedented cellular and circuit-level insights into neural mechanisms underlying contextual processing.
We first investigated how familiarity modifies the neural representation of stimuli in the mouse primary visual cortex (V1). Using silicon probe recordings and pupillometry, we probed neural activity in naive mice and after animals were exposed to the same stimulus over the course of several days. We have discovered that familiar stimuli evoke low-frequency oscillations in V1. Importantly, those oscillations were specific to the spatial frequency content of the familiar stimulus. To further validate our findings, we investigated how this novel form of visual learning is represented in serotonin-transporter (SERT) deficient mice. These transgenic animals have been previously found to have various neurophysiological alterations. We found that SERT-deficient animals showed longer oscillatory spiking activity and impaired cortical tuning after visual learning. Taken together, we discovered a novel phenomenon of familiarity-evoked oscillations in V1 and utilized it to reveal altered perceptual learning in SERT-deficient mice.
Next, we investigated how spatial context influences sensory processing. Visual illusions provide a great opportunity to investigate spatial contextual modulation in early visual areas. Leveraging behavioral training, high-density silicon probe recordings, and optogenetics, we provided evidence for an interplay of feedforward and feedback pathways during illusory processing in V1. We first designed an operant behavioral task to investigate illusory perception in mice. Kanizsa illusory contours paradigm was then adapted from primate studies to mouse V1 to elucidate neural correlates of illusory responses in V1. These experiments provided behavioral and neurophysiological evidence for illusory perception in mice. Using optogenetics, we then showed that suppression of the lateromedial area inhibits illusory responses in mouse V1. Taken together, we demonstrated illusory responses in mice and their dependence on the top-down feedback from higher-order visual areas.
Finally, we investigated how temporal context modulates neural responses by combining silicon probe recordings and a novel visual oddball paradigm that utilizes spatial frequency filtered stimuli. Our work extended prior oddball studies by investigating how adaptation and novelty processing depends on the tuning properties of neurons and their laminar position. Furthermore, given that reduced adaptation and sensory hypersensitivity are one of the hallmarks of altered sensory experiences in autism, we investigated the effects of temporal context on visual processing in V1 of a mouse model of fragile X syndrome (FX), a leading monogenetic cause of autism. We first showed that adaptation was modulated by tuning properties of neurons in both genotypes, however, it was more confined to neurons preferring the adapted feature in FX mice. Oddball responses, on the other hand, were modulated by the laminar position of the neurons in WT with the strongest novelty responses in superficial layers, however, they were uniformly distributed across the cortical column in FX animals. Lastly, we observed differential processing of omission responses in FX vs. WT mice. Overall, our findings suggest that reduced adaptation and increased oddball processing might contribute to altered perceptual experiences in FX and autism.
Neural Mechanisms of Predictive Impairments in Autism
National Institute of Mental HealthFind out more...
- Doctor of Philosophy
- Biological Sciences
- West Lafayette