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Joanne Chiu & Alesandra Martin - PhD Candidates

Titles: TBD

Faculty Evaluators: Angela Hewitt & Krishnan Padmanabhan

Student Moderator: Leah Sheppard

 Nov 18, 2024 @ 4:00 p.m.
 Medical Center | K-207 (2-6408)

Silei Zhu, MS - PhD Candidate, Neuroscience Graduate Program

In the early visual system, functional significance of the feedforward projection, from the retina to the dorsal lateral geniculate nucleus (LGN), and from LGN to the primary visual cortex (V1), is relatively well studied. In contrast, corticogeniculate (CG) feedback to LGN, which mainly originates from V1, is less well understood. Interestingly, CG feedback constitutes more than 30% of total synaptic input onto LGN neurons, outnumbering retinal feedforward synapses (5%-10%). The overall goal of my thesis is to study the behavioral effects of selective manipulation of CG feedback and to develop relevant methods. We first examined the effects of selective optogenetic suppression of CG neurons in anesthetized ferrets. Optogenetic suppression of CG feedback decreased activity among LGN neurons in the absence of visual stimulation but did not affect the visual responses of LGN neurons, suggesting that feedforward visual stimulus drive overrode weak corticogeniculate influence. Optogenetic effects on LGN and V1 neuronal responses depended on the frequency of LED illumination, with higher frequency illumination inducing slow oscillations in V1, dis-inhibiting V1 neurons locally, and producing more suppression among LGN neurons. We then trained ferrets to perform freely moving visual discrimination tasks and tracked their head and eye movements. Heading was predictive of choices as well as biases and decision strategies. While saccades also predicted choices, they were less predictive than heading and occurred after head turning. These findings characterize ferrets' head and eye movements during freely moving visual discrimination tasks and show that when unrestrained, ferrets orient first with their heads and then with their eye movements. Furthermore, these methods also provide a unique paradigm to probe the continuous process of visual decision-making in a more naturalistic manner. We also developed methods of long-term viral expression of genes of interest in ferrets. We injected AAV2 locally in V1 and confirmed viral expression in V1 neurons 14 months post-injection. However, AAV2-retro did not retrogradely label CG neurons after injection into ferret LGN. Instead, FuG-E lentivirus retrogradely infected CG neurons after injection into LGN and we confirmed viral gene expression 9 months post injection. Interestingly, FuG-E lentivirus barely labeled any neurons after local injection in V1. To determine the visual field affected by viral infection, we first mapped the retinotopy of ferret V1 on a ferret MRI brain atlas, and then registered virus expression patterns to this atlas to obtain the elevation and azimuth of each virus-infected neuron. We expressed inhibitory chemogenetic channels in V1 in one ferret but did not detect any behavioral effects of chemogenetic inactivation. To test the behavioral impact of optogenetic activation of CG neurons, we injected FuG-E lentivirus expressing ChR2 into LGN to label CG neurons in V1 retrogradely. After stimulation of CG neurons using wireless optogenetics during freely moving visual discrimination tasks, we detected a significant decrease of task performance in one ferret specifically in the visual field contralateral to the LGN injected with virus. However, at 10 months after the detection of behavioral changes, we did not detect viral expression in post-mortem histology. No significant behavioral effect was found in another animal 4-10 months post-injection, perhaps due to mismatch between the position of the visual stimulus and the retinotopic location of virus-infected neurons. Through these experiments, we learned the importance of completing behavioral tests within 1 year post viral injection to avoid expression decay, and the importance of developing methods to confirm success of viral expression and estimate affected receptive fields in vivo, e.g. using retinal imaging.

 Nov 21, 2024 @ 9:00 a.m.
 Medical Center | K307 (3-6408)

Matthew Adusei, MS - PhD Candidate, Neuroscience Graduate Program

Visual signals follow a feedforward progression: the dorsal lateral geniculate nucleus (LGN) receives and relays signals from the retina to primary visual cortex (V1). V1, in turn, provides reciprocal feedback to the LGN. Because the vast majority of LGN inputs target V1 (and secondary visual cortex or V2), their complementary corticogeniculate neurons are assumed to be similarly restricted to V1 and V2. However, there are direct inputs mainly from koniocellular LGN neurons to mid-level, extrastriate visual areas. Whether there are corticogeniculate neurons in mid-level extrastriate cortex that project to the LGN remains unknown. Additionally, since corticogeniculate neurons in V1 modulate the timing and precision of LGN responses, it would be important to investigate whether extrastriate corticogeniculate neurons serve analogous or different functions. In this thesis work, I investigate these unknown questions using virus-mediated gene delivery to 1) retrogradely trace corticogeniculate circuits and 2) optogenetically activate corticogeniculate feedback in primates and ferrets, carnivores with visual pathways similar to those in primates.

First, we identified and characterized the morphology of multiple distinct corticogeniculate neurons in mid-level extrastriate visual cortical areas of ferrets: posteromedial lateral suprasylvian (PMLS), posterolateral lateral suprasylvian (PLLS), and area 21a, and macaque monkeys: middle temporal (MT), medial superior temporal (MST), and area V4. Importantly, all three areas in both species were dominated by corticogeniculate neurons with spiny stellate morphology, suggesting possible preferential targeting of W/koniocellular LGN layers. We also observed corticogeniculate neurons in other extrastriate visual cortical areas, although we did not systematically characterize them.

Toward the second aim, we found that activating corticogeniculate feedback from PMLS in ferrets shifted the preferences of LGN neurons to low spatial and high temporal frequency stimuli, which aligns with the preference of PMLS neurons for fast-moving stimuli.

Together, our results suggest that: (1) extrastriate corticogeniculate feedback from PMLS may enhance LGN responses to fast-moving (high temporal frequency) stimuli, (2) evolutionary preservation of corticogeniculate neurons throughout visual cortex supports their critical role in visual function, (3) extrastriate geniculo-cortico-geniculate loops, that bypass V1, could provide a substrate for residual vision following V1 damage, (4) other sensory systems may contain corticothalamic neurons beyond primary and secondary sensory cortex that also target first order thalamus, (5) broader characterizations of these circuits could provide additional clues about the overall functional roles of corticothalamic feedback in sensory perception, and (6) the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay.

 Nov 22, 2024 @ 9:00 a.m.
 Medical Center | K207 (2-6408)

Emma Bryson, Yunshan Cai, & Alex Solorzano - PhD Candidates

Titles: TBD

Faculty Evaluators: Chris Holt & Harris Gelbard

Student Moderator: Nicole Popp

 Nov 25, 2024 @ 4:00 p.m.
 Medical Center | K-207 (2-6408)

Skylar DeWitt, Wen Li, & Gueladouan Jean Setenet - PhD Candidates

Titles: TBD

Faculty Evaluators: Liz Romanski & Jennetta Hammond

Student Moderator: Staci Rocco

 Dec 02, 2024 @ 4:00 p.m.
 Medical Center | K-207 (2-6408)

Tracey Preko, Pavel Rjabtsenkov, & Adam Roszczyk - PhD Candidates

Titles: TBD

Faculty Evaluators: Juliette McGreger & Chris Proschel

Student Moderator: Stacey Pedraza

 Dec 09, 2024 @ 4:00 p.m.
 Medical Center | K-207 (2-6408)