Institute of Neuroscience Faculty
Associate Professor, Dept. of Psychology
B.A. 1988, New College
Ph.D. 1996, New York University Medical Center
Cellular and molecular basis of memory.
HIPPOCAMPAL PLACE CELLS
The hippocampus, a structure deep in the medial temporal lobe of humans, forms new episodic memories, the sort of memories you most commonly think of like your memories for what you had for breakfast this morning, the concert you went to last week or your first day of college. Surprisingly, the rodent hippocampus closely resembles the human hippocampus, which make mice and rats appropriate model organisms for the study of episodic memory. Recording from hippocampal pyramidal neurons in awake, behaving rodents reveals their most obvious firing correlate: the animal’s position within a particular environment, earning them the name “place cells.” When exploring a novel environment, an animal’s hippocampal pyramidal neurons form their spatial receptive fields over a matter of minutes and generally stay stable thereafter. Therefore, the experience-dependent stabilization of place fields is an attractive candidate for studying the formation of hippocampal memory. However, precisely how the animal’s experience of a context translates into stable place fields remains largely unclear. We have found that the formation of stable place fields clearly requires direct experience with a space. This closely resembles how we recall the events in our lives: we see them through our own, first-person perspective. (See Rowland et al., 2011)
ANTERIOR CINGULATE 'OBJECT CELLS'
A wide variety of functions spanning motor and sensory information processing, memory, attention, novelty detection, and comparisons of expectation versus outcome engage the anterior cingulate cortex (ACC). We record ACC neuronal activity from freely behaving mice during tests of novel object and novel location recognition memory. During the novel location test, some neurons followed the familiar object to its new location, others fired exclusively where the object had been, and yet others fired to both current and former object locations. During tests of object recognition memory, introduction of the novel object elicits a change in firing to both the novel object and the remaining familiar object. Our ongoing research examines single-neuron correlates of objects in the rodent ACC and suggests that these neurons participate in constructing a mnemonic representation of salient elements within an environment. (See Weible et al., 2009)
ELUCIDATING THE CONNECTIVITY AND FUNCTION OF NEURAL CIRCUITS USING TRANGENIC MICE
Understanding how neural circuits work requires a detailed knowledge of cellular-level connectivity. The constraints of existing tools for transsynaptic tracing limit the resolution of our current understanding of neural circuitry. Some of the most intractable problems are a lack of cellular specificity of uptake, transport across multiple synaptic steps conflating direct and indirect inputs, and poor labeling of minor inputs. We use a novel combination of transgenic mouse technology and a recently developed tracing system based on rabies virus to overcome all three constraints. Fluorescent labeling from viral replication is restricted to defined neuronal cell types and their direct monosynaptic inputs. The fluorescence of label is similarly intense from cell to cell (see image to the right), making it an ideal tool for quantitative mapping of inputs to defined cell-types. Such neuron-specific tracing holds great promise for obtaining cellular-resolution wiring diagrams of the mammalian nervous system. (See Weible et al., 2010)
Understanding the connectivity is just the first step, however. We must also determine the contribution of the individual cell-types to the performance of the circuit, a difficult task because the circuits are comprised of intricately interwoven constellations of distinct cell-types. Towards this end, we recently began using novel optogenetic and pharmacogenetic tools to manipulate the activity of genetically-targeted cell populations. These tools will allow us to study the mammalian nervous system in the same way that you might study an electrical circuit: by removing the individual components and recording from other elements.
Rowland, D.C., Yanovich, Y., & Kentros, C.G. (2011) A stable hippocampal representation of a space requires its direct experience. PNAS.Weible AP, Schwarcz L, Wickersham IR, Deblander L, Wu H, Callaway EM, Seung HS, & Kentros CG. (2010) Transgenic targeting of recombinant rabies virus reveals monosynaptic connectivity of specific neurons. J Neurosci 30(49):16509-13.
Weible, A.P., Rowland, D.C., Pang, R., & Kentros, C.G. (2009) Neural correlates of novel object and novel location recognition behavior in the mouse anterior cingulate cortex. J Neurophysiology 102(4):2055-68.