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Cross campus path in winter
No full textCross campus path in winter. Photo by Olga Nilovahttps://digitalcommons.rockefeller.edu/the-evolving-campus/1052/thumbnail.jp
Mid-century opera glasses
No full textMid-century opera glasses and Rockefeller Institute concerts programs
Courtesy of Olga Nilova
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/the-evolving-campus/1067/thumbnail.jp
News & Notes, September 1969
No full textNews & Notes, September 1969
Full texthttps://digitalcommons.rockefeller.edu/the-evolving-campus/1069/thumbnail.jp
Marc Tessier-Lavigne and Bill de Blasio with a model of River Campus
No full textMarc Tessier-Lavigne and Bill de Blasio with a model of River Campus, March 2016.
From left: Glen, Fialkoff, Coles, de Blasio, Tessier-Lavigne, and O\u27Connor
Photo by Zach Veilleuxhttps://digitalcommons.rockefeller.edu/the-evolving-campus/1094/thumbnail.jp
Dopamine and the Temporal Dependence of Learning and Memory
Get PDFAnimal behavior is largely influenced by the seeking out of rewards and avoidance of punishments. Positive or negative reinforcements, like a food reward or painful shock, impart meaningful valence onto sensory cues in the animal\u27s environment. The ability of animals to form associations between a sensory cue and a rewarding or punishing reinforcement permits them to adapt their future behavior to maximize reward and minimize punishments. Animals rely on the timing of events to infer the causal relationships between cues and outcomes –– sensory cues that precede a painful shock in time become associated with its onset and are imparted with negative valence, whereas cues that follow the shock in time are instead associated with its cessation and imparted with positive valence. While the temporal requirements for associative learning have been well characterized at the behavioral level, the molecular and circuit mechanisms for this temporal sensitivity remain incompletely understood. Using the simple architecture of the mushroom body, an olfactory associative learning center in Drosophila, I examined how the relative timing of olfactory inputs and dopaminergic reinforcement signals is encoded at the molecular, synaptic, and circuit level to give rise to learned odor associations. I show that in Drosophila, opposing olfactory associations can be formed and updated on a trial-by-trial basis depending on the temporal relationship between an odor cue and dopaminergic reinforcement during conditioning. Additionally, both negative and positive reinforcements equivalently instruct appetitive and aversive olfactory associations –– odors preceding a negative reinforcement or following a rewarding reinforcement acquire an aversive valence, while odors instead following a negative reinforcement or preceding a rewarding reinforcement become attractive. Furthermore, functional imaging revealed that synapses within the mushroom body are bidirectionally modulated depending on the temporal ordering of odor and dopaminergic reinforcement, leading to synaptic depression when an odor precedes dopaminergic activity or synaptic facilitation when dopaminergic activity instead precedes an odor. Through the synchronous recording of neural activity and behavior, I found that the bidirectional regulation of synaptic transmission within the mushroom body directly correlates with the emergence of learned olfactory behaviors. This temporal sensitivity arises from two dopamine receptors, DopR1 and DopR2, that couple to distinct second-messengers and direct either synaptic depression or potentiation. Loss of either receptor renders the synapses of the mushroom body capable of only unidirectional plasticity and prevents the behavioral flexibility of writing opposing associations depending on the temporal structure of conditioning. Together, these results reveal how the distinct intracellular signaling pathways of two dopamine receptors can detect the order of events within an associative learning circuit to instruct opposing forms of synaptic and behavioral plasticity, providing a mechanism for animals to use both the onset and offset of a reinforcement signal to instruct distinct associations. Additionally, this bidirectional modulation allows animals to flexibly update olfactory associations on a trial-by-trial basis when temporal relationships are altered, permitting them to contend with a complex and changing sensory world
Distinct Populations of Layer 5B Pyramidal Neurons in the Primary Motor Cortex
Get PDFThe ability of motor cortex to plan, execute, and refine different movements depends on the coordinated activity of many neurons found across its laminar structure. Layer 5b (L5b), a deep cortical layer that drives output signals from the cortex, contains excitatory pyramidal neurons that innervate many subcortical areas of the brain. In the motor cortex, L5b is thicker and contains more pyramidal neurons than L5b of other cortical areas. Electrophysiological, anatomical, and RNA-Seq profiling of neurons in the motor cortex suggests there are diverse pyramidal neuron types within L5b. However, the precise identities of these distinct populations and their defining traits have been difficult to assess. Determining the cell type-specific properties of distinct L5b pyramidal neurons will not only help in understanding how the motor cortex is able to execute its varied functions, but may also reveal how selective vulnerability is established in neurodegenerative diseases that affect the motor cortex, such as Amyotrophic Lateral Sclerosis (ALS). Despite being expressed in all cells of the body, mutations associated with ALS lead to specific loss of LMNs in the brainstem and the ventral horn of the spinal cord, and UMNs in L5b of the motor cortex. For this reason, it is important to characterize the unique molecular profiles that may underlie an increased vulnerability of these cell Ph.D. types to the ubiquitously expressed mutations. In the motor cortex, this requires us to determine the characteristics that differentiate vulnerable L5b cells from other resistant cell types in the same area, and understand how these features may contribute to their death in ALS. This study aims to understand how anatomical traits and molecular properties, defined at the level of gene expression, vary across subpopulations of L5b pyramidal neurons in the motor cortex. We show that there are two distinct, but closely related, pyramidal neuron subtypes in mouse primary motor cortex which occupy discrete sublayers of L5b. In the SOD1-G93A mouse model of ALS, we observe loss of only one of these cell types, establishing the other as an analogous resistant L5b population. Using TRAP (Translating Ribosome Affinity Purification) with RNA-Seq, we show that these cells have important baseline differences in gene expression in healthy tissues, and that they display differential molecular responses to SOD1-G93A expression. Together, these findings reveal that the gene expression differences between the distinct L5b populations not only reflect their diverse cortical and subcortical anatomy, but may also establish selective vulnerability in ALS
Historic Laboratory. View no.17, January 2019
No full textThe reconstructed Historic laboratory on the 1st floor of the Flexner Hall, 2019
Photo by Zach Veilleuxhttps://digitalcommons.rockefeller.edu/historic-laboratory/1030/thumbnail.jp
Historic Laboratory. View no.15, January 2019
No full textFume hood in the historic laboratory. Flexner Hall, 1st floor, 2019
Photo by Zach Veilleuxhttps://digitalcommons.rockefeller.edu/historic-laboratory/1028/thumbnail.jp
Historic Laboratory. View no.13, January 2019
No full textBench in the historic laboratory. Flexner Hall, 1st floor, 2019
Photo by Zach Veilleuxhttps://digitalcommons.rockefeller.edu/historic-laboratory/1026/thumbnail.jp
Lewis Thomas Prize, 2019
Get PDF2019 Lewis Thomas Prize program
Recipient: Siddhartha Mukherjee
About the Lewis Thomas Prizehttps://digitalcommons.rockefeller.edu/artifacts-ephemera/1015/thumbnail.jp