Thesis Seminars

Matthew Adusei - PhD Candidate

Thesis Proposal - Advisor: Farran Briggs, PhD

In the visual system, geniculocortical projection neurons in the visual thalamus, the dorsal lateral geniculate nucleus (LGN), convey distinct visual information coming from the retina mainly to the primary visual cortex (V1) (Callaway 2005, Kaplan 2004, Sherman & Guillery 2006). From V1, visual information is passed on to extrastriate cortical areas along the visual cortical hierarchy (Felleman & Van Essen 1991). However, there are sparse V1-bypassing projections from the LGN to extrastriate visual cortical areas which are thought to originate primarily from cells within the koniocellular and C layers of the LGN (Dell et al 2018, Lyon & Rabideau 2012, Lysakowski et al 1988, Sherk 1986, Sincich et al 2004, Tong et al 1982). Visual perception likely involves reciprocal feedback circuits connecting the cortex with the LGN, which complement the feedforward geniculocortical projections. Using virus-mediated retrograde tracing techniques, we have identified and characterized multiple morphologically distinct corticogeniculate subtypes, predominantly in area 17 (V1) and area 18 (V2) (Briggs et al 2016, Hasse et al 2019), as well as in extrastriate visual cortical areas V4, MT and MST in macaques, and area 21a, PMLS, and PLLS, in ferrets. Physiological evidence based on axon conduction latencies and visual responses properties suggests that distinct V1 corticogeniculate subtypes align with the feedforward parallel processing streams (Briggs & Usrey 2005, Briggs & Usrey 2007, Briggs & Usrey 2009). Whether extrastriate corticogeniculate neurons are similarly functionally distinct and stream-specific is not known. Importantly, the presence of complementary, reciprocal, V1-independent connections between the LGN and extrastriate visual cortex, in ferrets and macaques, could provide a substrate for residual vision following V1 damage.
For my thesis project, I will investigate the functional role of the corticogeniculate feedback circuits that connect extrastriate visual areas with the LGN. I will investigate this by pursuing two aims using ferrets as an animal model. The first aim will investigate the functional role of extrastriate corticogeniculate neurons in regulating the activity of LGN neurons in the intact animal using a combination of virus-mediated gene delivery, optogenetics and electrophysiology. I hypothesize that extrastriate corticogeniculate neurons connect to LGN neurons in a stream-specific manner, consistent with our morphological data. I hypothesize that optogenetic activation of extrastriate corticogeniculate neurons will reduce response latencies and increase spike-timing precision among LGN neurons to which they connect. After shorter (~1 week, acute) and longer (~1 month, chronic) durations following V1 lesions, I hypothesize that there will be a progressive increase in the activity of extrastriate corticogeniculate neurons aligned with the W stream (similar to koniocellular stream) compared to intact animals. This hypothesis is supported by results from Schmid et al. (2009) suggesting that the koniocellular V1-bypassing pathway may be strengthened from a modulatory to a driving role post V1-damage. In the second aim, we will explore physiological changes among LGN, PMLS, PLLS, and area 21a neurons over time following V1 lesions. We will train ferrets to discriminate contrast, temporal frequency, spatial frequency, and direction changes among moving visual stimuli. We hypothesize that physiological changes in each area may depend on the type of visual discrimination tasks performed by the animals. Furthermore, we predict that changes in physiological properties of extrastriate corticogeniculate neurons following V1 lesions (observed in Aim 1) may dictate the changes we observe in the LGN and extrastriate areas. Altogether, these results will help us assess the functional significance of sparse extrastriate corticogeniculate projections, and

 Sep 24, 2021 @ 1:00 p.m.

Johanna Fritzinger - PhD Candidate, Thesis Proposal - Advisor: Laurel Carney, PhD

Timbre, the quality that allows sounds to be distinguished when they are identical in pitch, level, and duration, is a critical aspect of speech comprehension and music enjoyment. My proposal will fill a gap in neural studies of timbre by investigating how underlying mechanisms of encoding lead to robust representations of suprathreshold synthetic and natural instrument timbre in the inferior colliculus (IC). To test our hypotheses, we will record single-unit IC responses from awake Dutch-belted rabbits. We will also develop a new computational IC model based on physiological responses.
The spectral envelope of a harmonic sound is correlated with the timbral perception of “brightness”. We propose two mechanisms that contribute to spectral envelope encoding in the IC: capture and off-characteristic frequency (CF) inhibition. The first mechanism, capture, refers to a reduction of neural fluctuations, or the low-frequency changes in firing rate, of auditory-nerve fibers. Capture occurs when inner-hair-cell responses saturate due to a tone presented near their CF. IC neurons are sensitive to neural fluctuations, as characterized by modulation transfer functions in response to amplitude-modulated sounds. Preliminary results indicate that spectral peaks of synthetic timbre stimuli capture peripheral responses, leading to a rate representation of salient spectral features in the midbrain. The second mechanism is off-CF inhibition, which has been proposed to explain frequency-sweep sensitivity and psychophysical forward masking. Exciting preliminary responses to wideband tone-in-noise stimuli show inhibitory sidebands consistent with off-CF inhibition. A computational model that features capture, but not off-CF inhibition, was not able to predict responses to wideband tone-in-noise, indicating the need to add complexity to the model.
We have designed a set of experiments to test the hypothesis that the timbre of synthetic and instrument sounds is robustly encoded in the midbrain via capture and off-CF inhibition. In Aim 1, we hypothesize that the influences of capture and off-CF inhibition can be teased apart by recording single-unit responses to binaural or contralateral wideband tone-in-noise stimuli. We will update our computational model of the IC by adding off-CF inhibition and fitting the model to physiological responses. Aim 2 will test the hypothesis that the spectral peak of a shaped harmonic complex, synthetic timbre, is robustly encoded in the inferior colliculus over a range of suprathreshold levels. Aim 3 bridges the gap between synthetic and natural timbre by recording physiological responses to real instrument sounds. Responses from Aim 1 and Aim 2 will be used to further test the accuracy of the off-CF inhibition model. This project will provide insight on suprathreshold encoding of timbre, and the computational models created can be used for further research into hearing loss. Currently hearing aids and cochlear implants are not able to convey timbre well, and this research could lead to the improvement of these devices.

 Sep 29, 2021 @ 11:00 a.m.

Michael Duhain - PhD Candidate, Thesis Proposal - Advisers: Manuel Gomex-Ramirez & Kuan Wang

Object sensing and manipulation (i.e. haptics) requires discriminating a myriad of tactile features through the sense of touch. Key to this process are mechanisms of feature-based attention, which provide preferential processing of attended sensory features, while filtering out sensory information encoding non-relevant features. A previous study showed that selection of behaviorally relevant features is represented in the synchronized spiking between neurons tuned for the attended feature. The study further showed that increases in synchronized spiking were associated with enhanced performance. Yet, although this study showed how the brain enables selection of neural signals encoding the relevant features in the somatosensory system, the underlying circuit mechanism generating this feature-specific spike synchrony effect is yet to be elucidated. Fast scale coordinated spiking in neuronal populations is thought to be mediated by the activity of parvalbumin (PV) expressing inhibitory interneurons. Furthermore, in visual cortex, PV neurons are known to selectively respond to visual features (e.g., orientation and spatial frequency). Based on these findings, I propose that feature-specific spike synchrony in the somatosensory system is generated by a parvalbumin (PV) and pyramidal microcircuit (PvPy), whose cells are tuned for the same tactile feature. In this circuit, feature tuned PV interneurons generate inhibition of similarly tuned excitatory cells that is followed by a short window of high spiking probability between feature tuned pyramidal ensembles. I hypothesize that feature selection controls the coordinated spiking dynamics within a PvPy circuit to enhance representations of selected features in local neuronal populations, and facilitate interareal communication between functional subgroups in primary (S1) and secondary (S2) somatosensory cortex. To test the validity of this circuit and its dynamics, I trained mice to perform a 2-alternative forced-choice task that requires a response to a change in vibration frequency of a tactile stimulus delivered to the forepaws. Animals are visually cued to discriminate stimuli at one paw, while ignoring all stimuli at the uncued paw. In aim 1 of this project, I systematically test that the proposed PvPy circuit generates feature-specific spike synchrony effects in S1. In aim 2, I test how feature-specific spike synchrony drives interareal communication between functional subgroups of neurons. These aims will be accomplished in behaving animals through a series of experiments consisting of electrophysiological recordings with multi-laminar electrode arrays, in vivo 2-photon calcium imaging of specific neuronal populations, and optogenetics. Overall, this project aims to critically evaluate the presence of a novel functional circuit (PvPy) within somatosensory cortex that implements feature-based attention to enable preferential processing of selected features within local and across cortical areas.

 Sep 29, 2021 @ 2:00 p.m.