Past events

Drinking enough water is commonly recommended for health, but drinking too much water is dangerous. Therefore, animals have evolved sophisticated mechanisms to prevent harmful overhydration: for one thing, excess intake of water rapidly makes us feel nauseated and avoid further drinking. How do neural circuits mediate this phenomenon? To shed light on this question, we first identified a genetically defined subpopulation of neurons in the parabrachial nucleus (PB) that is activated by water intake. Using fiber photometry, we show that these neurons are activated by the ingestion of fluids, but not solids, and the responses are time-locked to the onset and offset of drinking. Extensive sets of recording experiments demonstrate that the detection mechanism for fluid intake is likely mechanosensory, and the fluid intake signals originate from all parts of the upper digestive tract. By manipulating the activity of the PB neurons, we establish that these neurons are both sufficient and necessary for limiting fluid intake, possibly by recruiting the projection to the median preoptic area. Together, our results identify 1) a central circuit node that can signal and limit fluid intake, 2) the detection mechanism for fluid intake in the periphery, and 3) the neural pathways by which the fluid intake signals are transmitted to the central nervous system.

Acquisition of motor skills often involves the concatenation of single movements into sequences. Along the course of learning, sequential performance becomes progressively faster and smoother, presumably by optimization of both motor planning and motor execution. Following its encoding during training, “how-to” memory undergoes consolidation, reflecting transformations in performance and its neurobiological underpinnings over time. This offline post-training memory process is characterized by two phenomena: reduced sensitivity to interference and the emergence of delayed, typically overnight, gains in performance. Successful learning is a result of strict control (gating) over the on-line and off-line stages of the experience-driven changes in the brain’s organization (neural plasticity). Factors, such as the amount of practice, the passage of time and the affordance of sleep and factors specific to the learning environment may selectively affect, – block or accelerate, - the expression of delayed gains in motor performance. These factors interact in a complex, non-linear manner. Developmental and inter-individual differences impose additional constraints on memory processes (e.g., age, chronotype, clinical condition). High-level reorganization of the movements as a unit following practice was shown to be subserved by optimization of planning and execution of individual movements. Temporal and kinematic analysis of performance demonstrated that only the offline inter-movement interval shortening (co-articulation) is selectively blocked by the interference experience, while velocity and amplitude, comprising movement time, are interference–insensitive. Sleep, including a day-time sleep, reduces the susceptibility of the memory trace to retroactive behavioural interference and also accelerates the expression of delayed gains in performance. Activity in cortico-striatal areas that was disrupted during the day due to interference and accentuated in the absence of a day-time sleep is restored overnight. Additional line of experiments showed that on-line environmental noise during training (vibro-auditory task-irrelevant stimulation) may be an important modulator of memory consolidation; its impact is ambiguous, presumably contingent on baseline arousal levels of the individual. 1. Albouy G., King B. R., Schmidt C., Desseilles M., Dang-Vu T., Balteau E., Phillips C., Degueldre C., Orban P., Benali H., Peigneux P., Luxen A., Karni A., Doyon J., Maquet P., Korman M. 2016 Cerebral Activity Associated with Transient Sleep-Facilitated Reduction in Motor Memory Vulnerability to Interference Scientific Reports 6:34948 2. Friedman J., Korman M. 2016 Offline optimization of the relative timing of movements in a sequence is blocked by behavioral retroactive interference Frontiers in Human Neuroscience, 10:623 3. Korman M., Herling Z., Levy I., Egbarieh N., Engel-Yeger B., Karni A. 2017 Background matters: minor vibratory sensory stimulation during motor skill acquisition selectively reduces off-line memory consolidation. Neurobiology of Learning and Memory 140:27-32

A theory of cortical function is proposed, based on a family of recurrent neural circuits, called ORGaNICs (Oscillatory Recurrent GAted Neural Integrator Circuits). The theory is applied to working memory and motor control. Working memory is a cognitive process for temporarily maintaining and manipulating information. Most empirical neuroscience research on working memory has measured sustained activity during delayed-response tasks, and most models of working memory are designed to explain sustained activity. But this focus on sustained activity (i.e., maintenance) ignores manipulation, and there are a variety of experimental results that are difficult to reconcile with sustained activity. ORGaNICs can be used to explain the complex dynamics of activity, and ORGaNICs can be use to manipulate (as well as maintain) information during a working memory task. The theory provides a means for reading out information from the dynamically varying responses at any point in time, in spite of the complex dynamics. When applied to motor systems, ORGaNICs can be used to convert spatial patterns of premotor activity to temporal profiles of motor activity: different spatial patterns of premotor activity evoke different temporal response dynamics. ORGaNICs offer a novel conceptual framework; Rethinking cortical computation in these terms should have widespread implications, motivating a variety of experiments.

Acquisition of motor skills often involves the concatenation of single movements into sequences. Along the course of learning, sequential performance becomes progressively faster and smoother, presumably by optimization of both motor planning and motor execution. Following its encoding during training, “how-to” memory undergoes consolidation, reflecting transformations in performance and its neurobiological underpinnings over time. This offline post-training memory process is characterized by two phenomena: reduced sensitivity to interference and the emergence of delayed, typically overnight, gains in performance. Successful learning is a result of strict control (gating) over the on-line and off-line stages of the experience-driven changes in the brain’s organization (neural plasticity). Factors, such as the amount of practice, the passage of time and the affordance of sleep and factors specific to the learning environment may selectively affect, – block or accelerate, - the expression of delayed gains in motor performance. These factors interact in a complex, non-linear manner. Developmental and inter-individual differences impose additional constraints on memory processes (e.g., age, chronotype, clinical condition). High-level reorganization of the movements as a unit following practice was shown to be subserved by optimization of planning and execution of individual movements. Temporal and kinematic analysis of performance demonstrated that only the offline inter-movement interval shortening (co-articulation) is selectively blocked by the interference experience, while velocity and amplitude, comprising movement time, are interference–insensitive. Sleep, including a day-time sleep, reduces the susceptibility of the memory trace to retroactive behavioural interference and also accelerates the expression of delayed gains in performance. Activity in cortico-striatal areas that was disrupted during the day due to interference and accentuated in the absence of a day-time sleep is restored overnight. Additional line of experiments showed that on-line environmental noise during training (vibro-auditory task-irrelevant stimulation) may be an important modulator of memory consolidation; its impact is ambiguous, presumably contingent on baseline arousal levels of the individual. 1. Albouy G., King B. R., Schmidt C., Desseilles M., Dang-Vu T., Balteau E., Phillips C., Degueldre C., Orban P., Benali H., Peigneux P., Luxen A., Karni A., Doyon J., Maquet P., Korman M. 2016 Cerebral Activity Associated with Transient Sleep-Facilitated Reduction in Motor Memory Vulnerability to Interference Scientific Reports 6:34948 2. Friedman J., Korman M. 2016 Offline optimization of the relative timing of movements in a sequence is blocked by behavioral retroactive interference Frontiers in Human Neuroscience, 10:623 3. Korman M., Herling Z., Levy I., Egbarieh N., Engel-Yeger B., Karni A. 2017 Background matters: minor vibratory sensory stimulation during motor skill acquisition selectively reduces off-line memory consolidation. Neurobiology of Learning and Memory 140:27-32

A theory of cortical function is proposed, based on a family of recurrent neural circuits, called ORGaNICs (Oscillatory Recurrent GAted Neural Integrator Circuits). The theory is applied to working memory and motor control. Working memory is a cognitive process for temporarily maintaining and manipulating information. Most empirical neuroscience research on working memory has measured sustained activity during delayed-response tasks, and most models of working memory are designed to explain sustained activity. But this focus on sustained activity (i.e., maintenance) ignores manipulation, and there are a variety of experimental results that are difficult to reconcile with sustained activity. ORGaNICs can be used to explain the complex dynamics of activity, and ORGaNICs can be use to manipulate (as well as maintain) information during a working memory task. The theory provides a means for reading out information from the dynamically varying responses at any point in time, in spite of the complex dynamics. When applied to motor systems, ORGaNICs can be used to convert spatial patterns of premotor activity to temporal profiles of motor activity: different spatial patterns of premotor activity evoke different temporal response dynamics. ORGaNICs offer a novel conceptual framework; Rethinking cortical computation in these terms should have widespread implications, motivating a variety of experiments.

How is reliable physiological function maintained in cells despite considerable variability in the values of key parameters of multiple interacting processes that govern that function? I will describe a possible approach to the problem, through analysis of the classic Hodgkin-Huxley formulation of membrane action potential. Although the full Hodgkin-Huxley model is very sensitive to fluctuations that independently occur in its many parameters, the outcome is in fact determined by simple combinations of these parameters along two physiological dimensions: Structural and Kinetic (denoted S and K). The impacts of parametric fluctuations on the dynamics of the system — seemingly complex in the high dimensional representation of the Hodgkin-Huxley model — are tractable when examined within the S-K plane. Experimental validation of the resulting phase diagram is offered, using a bio-synthetic system.