My long term career goal is to establish an independent research program aimed at leveraging cutting-edge optical technologies available in mice to study neural circuits underlying cognitive functions. To facilitate this goal, I have received training in a variety of techniques including cellular neurophysiology, functional two-photon microscopy, and viral-based circuit tracing. During the mentored phase of this award, I will work under the supervision of Professor Mriganka Sur, a pioneer in optical methods for interrogation of neural circuits, with advice from a mentoring team consisting of Professors Ann Graybiel, Kay Tye, and Wasim Malik. Additional training in behavioral task design, projection-specific optogenetic manipulations, and computational methods for data analysis from these mentors will equip me with the tools necessary to probe neural underpinnings of cognitive functions and springboard me to an independent career. This work will be done at the Brain and Cognitive Sciences department at MIT, which offers both expansive infrastructural resources and a vibrant intellectual community necessary for making fundamental discoveries on the circuit-basis of behavior. During my NRSA-sponsored postdoctoral training, I identified a crucial role for visual cortical inputs to the anterior cingulate subdivision of the prefrontal cortex (PFC) in visual decision making. My immediate goal is to ascertain exactly which cognitive functions are supported by this area and the underlying circuit-level mechanisms. While the PFC has been widely implicated in guiding attention and motor planning, it is unclear if the same or distinct neural substrates underlie these functions. According to the ?pre-motor theory of attention?, attention is an emergent property of networks that implement actions and, hence, the same set of neurons contribute to both attention and motor planning. However, recent evidence suggests that these functions are served by distinct cell-types. In this K99 application, I will test the hypothesis that distinct PFC cell-types target either the visual cortex or superior colliculus, a midbrain structure that coordinates motor behavior, to guide attentional modulation of sensory processing or motor planning, respectively.
In Aim 1, I will use optogenetic inactivation to test the contribution of visual cortex, superior colliculus, or PFC to performance on a novel two-choice visual task with specific temporal epochs for attentional engagement or motor planning.
(Aim 2 a) Next, I will use projection-specific optogenetic inactivation to test the hypothesis that PFC cell- types that project to visual cortex contribute to attentional processing of visual stimuli, whereas cells projecting to superior colliculus contribute to motor planning.
(Aim 2 b) Using two-photon microscopy, I will measure the neural signatures of attentional engagement and motor planning in these two cell-types.
(Aim 3) In the independent phase of the award, I will use a viral-based disynaptic tracing strategy to identify the sources of inputs onto specific projection cell-types in the PFC. Using dual-color two-photon microscopy and optogenetic inhibition, I will determine how long-range input axons contribute to neural coding of task variables by specific PFC projection cell-types Together, these studies will clarify circuit-level mechanisms of PFC contributions to attention and motor planning.
Dysregulation of attention and motor planning is implicated in various human disorders, including attention deficit hypersensitivity disorder (ADHD), dyspraxia, and apraxia caused by neurological damage. In this application, we will study cell type-specific PFC circuits that contribute to attention and motor planning. A thorough understanding of neural mechanisms underlying these cognitive abilities may clarify what goes awry during disease states and may help identify novel targets for therapeutic interventions for these ailments.
|Huda, Rafiq; Goard, Michael J; Pho, Gerald N et al. (2018) Neural mechanisms of sensorimotor transformation and action selection. Eur J Neurosci :|
|Bloem, Bernard; Huda, Rafiq; Sur, Mriganka et al. (2017) Two-photon imaging in mice shows striosomes and matrix have overlapping but differential reinforcement-related responses. Elife 6:|