Basic Life Science Research Associate, Biology
Current Research and Scholarly Interests
As a postdoctoral research fellow in the laboratory of Mark Schnitzer I am utilizing chronic, in vivo, fluorescence calcium-imaging combined with chemo and optogenetic manipulations to determine the mechanisms by which neuronal circuits and the ensembles of cells within them enable the encoding and recall of context-dependent memories. Memories are often constructed from associations between diverse pieces of information that have no intrinsic connection. By studying how disparate pieces of information are stored in relation to each other before and after a learning event, I hope to shed light on the mechanisms by which memories are formed in the mammalian brain. Ultimately, this research will facilitate our understanding of how higher order knowledge is synthesized and extracted from information in the brain.
Large-Scale Fluorescence Calcium-Imaging Methods for Studies of Long-Term Memory in Behaving Mammals
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
2016; 8 (5)
During long-term memory formation, cellular and molecular processes reshape how individual neurons respond to specific patterns of synaptic input. It remains poorly understood how such changes impact information processing across networks of mammalian neurons. To observe how networks encode, store, and retrieve information, neuroscientists must track the dynamics of large ensembles of individual cells in behaving animals, over timescales commensurate with long-term memory. Fluorescence Ca(2+)-imaging techniques can monitor hundreds of neurons in behaving mice, opening exciting avenues for studies of learning and memory at the network level. Genetically encoded Ca(2+) indicators allow neurons to be targeted by genetic type or connectivity. Chronic animal preparations permit repeated imaging of neural Ca(2+) dynamics over multiple weeks. Together, these capabilities should enable unprecedented analyses of how ensemble neural codes evolve throughout memory processing and provide new insights into how memories are organized in the brain.
View details for DOI 10.1101/cshperspect.a021824
View details for Web of Science ID 000377084600005
View details for PubMedID 27048190
Molecular and Cellular Mechanisms for Trapping and Activating Emotional Memories.
2016; 11 (8)
Recent findings suggest that memory allocation to specific neurons (i.e., neuronal allocation) in the amygdala is not random, but rather the transcription factor cAMP-response element binding protein (CREB) modulates this process, perhaps by regulating the transcription of channels that control neuronal excitability. Here, optogenetic studies in the mouse lateral amygdala (LA) were used to demonstrate that CREB and neuronal excitability regulate which neurons encode an emotional memory. To test the role of CREB in memory allocation, we overexpressed CREB in the lateral amygdala to recruit the encoding of an auditory-fear conditioning (AFC) memory to a subset of neurons. Then, post-training activation of these neurons with Channelrhodopsin-2 was sufficient to trigger recall of the memory for AFC, suggesting that CREB regulates memory allocation. To test the role of neuronal excitability in memory allocation, we used a step function opsin (SFO) to transiently increase neuronal excitability in a subset of LA neurons during AFC. Post-training activation of these neurons with Volvox Channelrhodopsin-1 was able to trigger recall of that memory. Importantly, our studies show that activation of the SFO did not affect AFC by either increasing anxiety or by strengthening the unconditioned stimulus. Our findings strongly support the hypothesis that CREB regulates memory allocation by modulating neuronal excitability.
View details for DOI 10.1371/journal.pone.0161655
View details for PubMedID 27579481
Encoding and storage of spatial information in the retrosplenial cortex
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2014; 111 (23): 8661-8666
The retrosplenial cortex (RSC) is part of a network of interconnected cortical, hippocampal, and thalamic structures harboring spatially modulated neurons. The RSC contains head direction cells and connects to the parahippocampal region and anterior thalamus. Manipulations of the RSC can affect spatial and contextual tasks. A considerable amount of evidence implicates the role of the RSC in spatial navigation, but it is unclear whether this structure actually encodes or stores spatial information. We used a transgenic mouse in which the expression of green fluorescent protein was under the control of the immediate early gene c-fos promoter as well as time-lapse two-photon in vivo imaging to monitor neuronal activation triggered by spatial learning in the Morris water maze. We uncovered a repetitive pattern of cell activation in the RSC consistent with the hypothesis that during spatial learning an experience-dependent memory trace is formed in this structure. In support of this hypothesis, we also report three other observations. First, temporary RSC inactivation disrupts performance in a spatial learning task. Second, we show that overexpressing the transcription factor CREB in the RSC with a viral vector, a manipulation known to enhance memory consolidation in other circuits, results in spatial memory enhancements. Third, silencing the viral CREB-expressing neurons with the allatostatin system occludes the spatial memory enhancement. Taken together, these results indicate that the retrosplenial cortex engages in the formation and storage of memory traces for spatial information.
View details for DOI 10.1073/pnas.1313222111
View details for Web of Science ID 000336976000083
View details for PubMedID 24912150
Synaptic tagging during memory allocation
NATURE REVIEWS NEUROSCIENCE
2014; 15 (3): 157-169
There is now compelling evidence that the allocation of memory to specific neurons (neuronal allocation) and synapses (synaptic allocation) in a neurocircuit is not random and that instead specific mechanisms, such as increases in neuronal excitability and synaptic tagging and capture, determine the exact sites where memories are stored. We propose an integrated view of these processes, such that neuronal allocation, synaptic tagging and capture, spine clustering and metaplasticity reflect related aspects of memory allocation mechanisms. Importantly, the properties of these mechanisms suggest a set of rules that profoundly affect how memories are stored and recalled.
View details for DOI 10.1038/nrn3667
View details for Web of Science ID 000331940100011
View details for PubMedID 24496410
CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala
2009; 12 (11): 1438-1443
The mechanisms that determine how information is allocated to specific regions and cells in the brain are important for memory capacity, storage and retrieval, but are poorly understood. We manipulated CREB in a subset of lateral amygdala neurons in mice with a modified herpes simplex virus (HSV) and reversibly inactivated transfected neurons with the Drosophila allatostatin G protein-coupled receptor (AlstR)/ligand system. We found that inactivation of the neurons transfected with HSV-CREB during training disrupted memory for tone conditioning, whereas inactivation of a similar proportion of transfected control neurons did not. Whole-cell recordings of fluorescently tagged transfected neurons revealed that neurons with higher CREB levels are more excitable than neighboring neurons and showed larger synaptic efficacy changes following conditioning. Our findings demonstrate that CREB modulates the allocation of fear memory to specific cells in lateral amygdala and suggest that neuronal excitability is important in this process.
View details for DOI 10.1038/nn.2405
View details for Web of Science ID 000271194100017
View details for PubMedID 19783993
Molecular and Cellular Approaches to Memory Allocation in Neural Circuits
2009; 326 (5951): 391-395
Although memory allocation is a subject of active research in computer science, little is known about how the brain allocates information within neural circuits. There is an extensive literature on how specific types of memory engage different parts of the brain, and how neurons in these regions process and store information. Until recently, however, the mechanisms that determine how specific cells and synapses within a neural circuit (and not their neighbors) are recruited during learning have received little attention. Recent findings suggest that memory allocation is not random, but rather specific mechanisms regulate where information is stored within a neural circuit. New methods that allow tagging, imaging, activation, and inactivation of neurons in behaving animals promise to revolutionize studies of brain circuits, including memory allocation. Results from these studies are likely to have a considerable impact on computer science, as well as on the understanding of memory and its disorders.
View details for DOI 10.1126/science.1174519
View details for Web of Science ID 000270818600043
View details for PubMedID 19833959