The effect of chronic stress on learning and memory - Damien Rei (Tsai...more
The effect of chronic stress on learning and memory - Damien Rei (Tsai lab)
Chronic stress, a risk factor for the learning and memory deficits in Alzheimer’s disease (AD), is mediated by the amygdala, the brain’s stress center. Postdoctoral associate Damien Rei combined optogenetics and inhibitory Gi-DREADD in mice to selectively activate and deactivateneurons in specific brain regions. He found that activating the basal lateral amygdala (BLA) mimics the detrimental effect of chronic stress on learning and memory, whereas inactivating it protects against these deficits. To translate the findings to the study of AD, Rei plans to see if activating or inactivating BLA accelerates or slows down the progression of the disease in mouse models of AD.
Fear memory recall - Steve Ramirez and Xu Liu (Tonegawa Lab)
To explore the cellular basis of fear memories, graduate student Steve Ramirez and postdoctoral associate Xu Liu combined optogenetics with a system for labeling the neurons that become active in the dentate gyrus (DG) of the hippocampus as mice learn to fear a particular scary context. Later, the researchers could activate just those neurons by pulsing light through tiny optic fibers implanted in the DG. This activation re-triggered the mice’s fear even while they were in a safe context. The ability to precisely control defined neurons that were activated during an event allows researchers to probe the underlying nature, and the spatial/temporal dynamics, of episodic memories.
Learning when to see what - Jeff Gavornik (Bear Lab)
Researchers have long assumed that V1, the first region of the primary cortex to process visual information, only recognizes the “where” of an image’s lines, edges and curves. But postdoctoral fellow Jeff Gavornik found that V1 also recognizes the “when” of images as they appear in temporal relation to other images. He trains mice on visual recognition tasks and shows them predictable sequences of visual stimuli while recording from V1 neurons. By then varying the sequences from what the mice learned to expect, he found that the brain predicts what will come next, suggesting that higher-order processing is already occurring very early in visual recognition.
Glial calcium signaling and neuronal hyperexcitability - Jan Melom (Littleton Lab)
Cortical glial cells, once considered mere helper cells, can actively contribute to brain function – and dysfunction, including seizures and epilepsy. Graduate student Jan Melom studies zydeco, a mutant Drosophila (fly) that “dances” when seizing upon changes in temperature or mechanical stimulation. She found that the zydeco gene affects a calcium exchanger at the membrane and eliminates normal calcium oscillations at the glial membrane, and that calmodulin is required for the seizures. She hypothesizes that acute disruption of calcium signaling in glia can impair neuronal function and lead to seizure, and she is identifying suppressors of zydeco that may translate to treating human disorders.
Translational regulation of neurogranin levels - Kendrick...more
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.