<p><a></a><a>The visual
system is capable of interpreting immense sensory complexity, allowing us to
quickly identify behaviorally relevant stimuli in the environment. It performs
this task with a hierarchical organization that works to detect, relay, and
integrate visual stimulus features into an interpretable form. To understand
the complexities of this system, visual neuroscientists have benefited from the
many advantages of using mice as visual models. Despite their poor visual acuity,
these animals possess surprisingly complex visual systems, and have been
instrumental in understanding how visual features are processed in the primary
visual cortex (V1). However, a growing body of literature has shown that
primary sensory areas like V1 are capable of more than basic feature detection,
but can express neural activity patterns related to learning, memory,
categorization, and prediction. </a></p>
<p>Visual
experience fundamentally changes the encoding and perception of visual stimuli
at many scales, and allows us to become familiar with
environmental cues. However, the neural
processes that govern visual familiarity are poorly understood. By exposing
awake mice to repetitively presented visual stimuli over several days, we
observed the emergence of low frequency
oscillations in the primary visual cortex (V1). The oscillations emerged in
population level responses known as visually evoked potentials (VEPs), as well
as single-unit responses, and were not observed before the perceptual
experience had occurred. They were also not evoked by novel visual stimuli,
suggesting that they represent a new form of visual familiarity in the form of
low frequency oscillations. The oscillations also required the muscarinic
acetylcholine receptors (mAChRs) for
their induction and expression, highlighting the importance of the cholinergic
system in this learning and memory-based phenomenon. Ongoing visually evoked
oscillations were also shown to increase the VEP amplitude of incoming visual
stimuli if the stimuli were presented at the high excitability phase of the
oscillations, demonstrating how neural activity with unique temporal dynamics
can be used to influence visual processing.</p>
<p>Given the necessity of
perceptual experience for the strong expression of these oscillations and their
dependence on the cholinergic system, it was clear we had discovered a
phenomenon grounded in visual learning or memory. To further validate this, we
characterized this response in a mouse model of Fragile X syndrome (FX), the
most common inherited form of autism and a condition with known visual
perceptual learning deficits. Using a multifaceted experimental approach, a
number of neurophysiological differences were found in the oscillations displayed
in FX mice. Extracellular recordings revealed shorter durations and lower power
oscillatory activity in FX mice. Furthermore, we found that the frequency of
peak oscillatory activity was significantly decreased in FX mice, demonstrating
a unique temporal neural impairment not previously reported in FX. In
collaboration with Dr. Christopher J. Quinn at Purdue, we performed functional
connectivity analysis on the extracellularly recorded spikes from WT and FX
mice. This analysis revealed significant impairments in functional connections
from multiple layers in FX mice after the perceptual experience; some of which
were validated by another graduate student (Qiuyu Wu) using Channelrhodopsin-2
assisted circuit mapping (CRACM). Together, these results shed new light on how
visual stimulus familiarity is differentially encoded in FX via persistent
oscillations, and allowed us to identify impairments in cross layer
connectivity that may underlie these differences. </p>
<p>Finally,
we asked whether these oscillations are observable in other brain areas or are intrinsic
to V1. Furthermore, we sought to determine if the oscillating unit populations
in V1 possess uniform firing dynamics, or contribute differentially to the
population level response. By performing paired recordings, we did not find
prominent oscillatory activity in two visual thalamic nuclei (dLGN and LP) or a
nonvisual area (RSC) connected to V1, suggesting the oscillations may not
propagate with similar dynamics via cortico-thalamic connections or
retrosplenial connections, <a>but may either be uniquely distributed
across the visual hierarchy or predominantly</a> restricted to V1. Using
K-means clustering on a large population of oscillating units in V1, we found
unique temporal profiles of visually evoked responses, demonstrating distinct
contributions of different unit sub-populations to the oscillation response
dynamics.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/11323526 |
| Date | 06 December 2019 |
| Creators | Samuel T Kissinger (8086100) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Visual_experience-dependent_oscillations_in_the_mouse_visual_system/11323526 |
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