Translational regulation of neurogranin levels - Kendrick Jones (Xu Lab)
How do levels of neurogranin, a protein that regulates calcium signaling in neurons, vary in response to experi- ence? Postdoctoral associate Kendrick Jones showed that in mice, the experience of acute fear enhances neurogranin levels in the hippocampus. In cultured cortical neurons that were activated to recapitulate that experience-de- pendent increase, adding norepinephrine enhanced the size and speed of this neurogranin increase via the new translation of pre-existing mRNA. Also, increasing neu- rogranin levels in hippocampal slices led to an increase in neuronal excitability, while decreasing neurogranin re- duced excitability. Jones is now investigating the impact of manipulating neurogranin levels on behavior in mice.
Thalamus and hippocampus during slow wave sleep - Hector Penagos (Wilson Lab)
Matt Wilson’s lab previously showed that during slow wave sleep, hippocampal place cells replay the firing pat- terns that developed as a rat ran a maze. Postdoctoral as- sociate Hector Penagos looks at the less-studied role of the anterior thalamus in episodic memory and spatial navigation. He recorded from both “head direction cells” in the thalamus and hippocampal place cells as rats navi- gated a maze and later dreamed about. When place cells burst during sleep, head direction cells were silent, and visa versa, as if they were taking turns talking and listen- ing. Penagos is now investigating how thalamus cells bias what the hippocampus encodes and influence the content of the hippocampal replay.
Visualization of synaptic dynamics in vivo - Katie Villa (Nedivi Lab)
The connections between neurons change over time, enabling new learning and memory to occur. Previous- ly, the Nedivi Lab found that excitatory dendritic arbors remain stable while inhibitory dendrites and axons are plastic, constantly remodeling their connections with ex- citatory cells. Graduate student Katie Villa, working with former graduate student Jerry Chen and current gradu- ate student Kalen Berry, developed a technique for visu- alizing inhibitory synapses on excitatory cells over time. These images revealed the dynamic rearrangement of in- hibitory synapses on the dendritic shafts and spines, and showed that changes in inhibitory synapses are coordi- nated with changes in excitatory spines.
Novel pathways for optogenetic control of anxiety - Ada Felix-Ortiz (Tye Lab)
Kay Tye’s lab has been up and running for just five months, and for its first presentation at a Picower retreat, research associate Ada Felix-Ortiz presented new preliminary data from optogenetic experiments looking at parallel circuits involved in anxiety. She uses optogenetic projection-specific targeting techniques to investigate the inputs from the basolateral amygdala to cortical and hip- pocampal regions. Felix-Ortiz will next combine optoge- netics with electrophysiology to provide a systems-level mechanistic explanation of this behavioral phenomenon.
Synchronous neural ensembles for rules - Eric Denovellis (Miller Lab)
What are the neural mechanisms that support our flex- ibility in applying rules of behavior to different situations? With collaborators in the Miller Lab, research affiliate Eric Denovellis recorded from neurons in the prefrontal cor- tex (PFC) while monkeys switched between two rules: at- tending to an image’s color versus its orientation (the more dominant rule). Analyzing the oscillatory synchroniza- tion that encoded each rule showed that beta-frequency synchrony selects the relevant rule ensemble, while alpha- frequency de-selects a stronger, but currently irrelevant, rule. Denovellis proposes that synchronous activity in PFC is a mechanism that allows us to follow specific rules but to change dynamically as demands change.
Differential vulnerability in Huntington’s Disease - Robert Fenster (Heiman Lab)
Robert Fenster is a visiting scholar in the Myriam Hei- man Lab, which investigates the selective vulnerability of medium spiny neurons of the striatum and deep cerebral cortical neurons in Huntington’s Disease (HD). The ba- sis for this enhanced vulnerability is unknown, but could potentially be targeted therapeutically. By analyzing cell- type specific information in a mouse model of HD, they demonstrated that the most vulnerable neurons express high levels of polyglutamine-containing proteins. They hypothesize that over-expression of polyglutamine pro- teins leads to the characteristic huntingtin aggregation and cell death in HD, and they have validated a primary culture model system to directly test this hypothesis.
Distinct cortical inhibitory networks in vivo - Caroline Runyan (Sur Lab)
Postdoctoral fellow Caroline Runyan has expanded upon work from Mriganka Sur’s lab that Nathan Wilson first reported at last year’s retreat. They use optogenet- ics to activate specific types of inhibitory cells, either as a population or one cell at a time, while using new func- tional imaging methods to measure the effects on visual responses in neighboring cells in the primary visual cor- tex. They are asking: what are the functional impacts of the activity of specific inhibitory cell types, and to which neurons in the local network do single inhibitory neurons functionally connect? Their findings suggest that inhibi- tory neuronal subclasses have distinct and complementary roles in cortical circuits.
