Faculty Bibliography

In humans and animal models, oxytocin increases social closeness, attachment and prosocial behaviors, while decreasing anxiety and stress levels. Efficiently triggering the release of endogenous oxytocin could serve as a powerful therapeutic intervention for disorders of social behavior and for anxiety. We designed a new version of a social sensorimotor synchronization task to investigate the role of social approval in inducing biochemical and psychological changes following behavioral synchrony in a sample of 80 college students. Social approval in the form of real time positive feedback increased well-being only in women, while increasing social closeness in both genders. Social disapproval in the form of real time negative feedback prevented a decrease in stress levels that otherwise women reported following engagement in either social or non-social synchronization. Surprisingly, for certain personality traits, negative social feedback during sensorimotor synchronization was psychologically beneficial irrespective of gender. Salivary oxytocin levels increased only in women after the social but not the non-social synchronization tasks. Oxytocin dynamics were independent of the type of real time feedback that subjects received, indicating the existence of distinct mechanisms for hormonal versus behavioral changes following synchronization. Nevertheless, changes in salivary oxytocin after positive social feedback correlated with changes in well-being and predicted changes in prosocial attitudes. Our findings show evidence of distinct mechanisms for behavioral versus hormonal changes following social sensorimotor synchronization, and indicate that gender and personality traits should be carefully considered when designing behavioral therapies for improving social attitudes and for stress management.

Background: Albuminuria is a risk factor for kidney disease progression and CV disease. We examined the relative and absolute effects of CANA by baseline albuminuria among CREDENCE participants.
Method(s): CREDENCE was a double-blind, randomized study of 4401 participants with eGFR 30-<90mL/min/1.73m2 and uACR >300-5000mg/g who demonstrated that CANA significantly reduced renal and CV outcomes, including the primary composite of end-stage kidney disease, doubling serum creatinine, or renal or CV death. We analyzed the effect of CANA on renal, CV, and safety outcomes by baseline uACR.
Result(s): At baseline, 2348 (53.4%), 1547 (35.2%), and 506 (11.5%) participants had uACR <=1000, >1000-<3000, >=3000mg/g. Higher uACR was associated with higher event rates (Figure). CANA reduced renal and CV endpoints, with no statistical variation by uACR (all p heterogeneity >0.17). CANA led to a greater absolute reduction in renal events in those with higher uACR (number needed to treat to prevent 1 episode of the primary composite: 22 and 8 for uACR >1000-<3000 and >=3000mg/g). Rates of renalrelated adverse events were lower with CANA, and the relative reduction was greater with higher uACR (p heterogeneity=0.003). CANA had no significant effect on acute kidney injury, volume depletion, hyperkalemia, urinary tract infections or hypoglycemia, with no differences by uACR (all p heterogeneity >0.12).
Conclusion(s): CANA safely reduces renal and CV events in people with type 2 diabetes and substantial albuminuria, with the greatest absolute renal benefit in those with uACR of 3000-5000mg/g

Purpose/UNASSIGNED:To revisit the "loopole," an unusual coil topology whose unbalanced current distribution captures both loop and electric dipole properties, which can be advantageous in ultra-high-field MRI. Methods/UNASSIGNED:Loopole coils were built by deliberately breaking the capacitor symmetry of traditional loop coils. The corresponding current distribution, transmit efficiency, and signal-to-noise ratio (SNR) were evaluated in simulation and experiments in comparison to those of loops and electric dipoles at 7 T (297 MHz). Results/UNASSIGNED:, the loopole demonstrated significant performance boost in either the transmit efficiency or SNR at the center of a dielectric sample when compared to a traditional loop. Modest improvements were observed when compared to an electric dipole. Conclusion/UNASSIGNED:The loopole can achieve high performance by supporting both divergence-free and curl-free current patterns, which are both significant contributors to the ultimate intrinsic performance at ultra-high field. While electric dipoles exhibit similar hybrid properties, loopoles maintain the engineering advantages of loops, such as geometric decoupling and reduced resonance frequency dependence on sample loading.

Normative models of neural computation offer simplified yet lucid mathematical descriptions of murky biological phenomena. Previously, online Principal Component Analysis (PCA) was used to model a network of single-compartment neurons accounting for weighted summation of upstream neural activity in the soma and Hebbian/anti-Hebbian synaptic learning rules. However, synaptic plasticity in biological neurons often depends on the integration of synaptic currents over a dendritic compartment rather than total current in the soma. Motivated by this observation, we model a pyramidal neuronal network using online Canonical Correlation Analysis (CCA). Given two related datasets represented by distal and proximal dendritic inputs, CCA projects them onto the subspace which maximizes the correlation between their projections. First, adopting a normative approach and starting from a single-channel CCA objective function, we derive an online gradient-based optimization algorithm whose steps can be interpreted as the operation of a pyramidal neuron. To model networks of pyramidal neurons, we introduce a novel multi-channel CCA objective function, and derive from it an online gradient-based optimization algorithm whose steps can be interpreted as the operation of a pyramidal neuron network including its architecture, dynamics, and synaptic learning rules. Next, we model a neuron with more than two dendritic compartments by deriving its operation from a known objective function for multi-view CCA. Finally, we confirm the functionality of our networks via numerical simulations. Overall, our work presents a simplified but informative abstraction of learning in a pyramidal neuron network, and demonstrates how such networks can integrate multiple sources of inputs.

Animals are capable of detecting odorants in a single sniff, at extremely low concentrations. This ability is crucial for survival, yet it is unknown how the olfactory system supports detection at the perceptual limit. In the mouse olfactory bulb, inhalation of different odors leads to changes in the set of neurons activated, as well as when neurons are activated relative to each other (synchrony), and the onset of inhalation (latency). A key question is which features of stimulus evoked activity (e.g. rate, synchrony, or latency) are used to guide detection behavior? Here, we probed the sensitivity of mice to perturbations across each stimulus dimension using holographic two-photon (2P) optogenetic stimulation of olfactory bulb neurons, with cellular and single action potential resolution and millisecond precision. We found that mice can detect single action potentials evoked synchronously across <20 olfactory bulb neurons. Mice exhibited this sensitivity for artificial ensembles of mitral cells, as well as mixed ensembles of mitral and granule cells. Further, we discovered that detection depends strongly on the synchrony of activation across neurons, with detectability falling to near-chance levels with an imposed stimulus spread 3 30 ms, while detection performance was minimally perturbed by changes in the latency of activation relative to inhalation. These results reveal that mice are acutely attuned to single neurons and action potentials in olfactory circuits, and that synchrony across neurons may be a critical feature supporting the perceptibility of sparse ensemble activity signals

Regulating gene expression at the protein level is becoming increasingly important for answering basic questions in neurobiology. Several techniques using destabilizing domains (DD) on transgenes, which can be activated or deactivated by specific drugs, have been developed to achieve this goal. A DD from bacterial dihydrofolate reductase bound and stabilized by trimethoprim (TMP) represents such a tool. To control transgenic protein levels in the brain, the DD-regulating drugs need to have sufficient penetration into the central nervous system (CNS). Yet, very limited information is available on TMP pharmacokinetics in the CNS following systemic injection. Here, we performed a pharmacokinetic study on the penetration of TMP into different CNS compartments in the rat. We used mass spectrometry to measure TMP concentrations in serum, cerebrospinal fluid (CSF) and tissue samples of different CNS regions upon intraperitoneal TMP injection. We show that TMP quickly (within 10 min) penetrates from serum to CSF through the blood-CSF barrier. TMP also shows quick penetration into brain tissue but concentrations were an order of magnitude lower compared to serum or CSF. TMP concentration in spinal cord was lower than in any other analyzed CNS area. Nevertheless, effective levels of TMP to stabilize DDs can be reached in the CNS with half-lives around 2 h. These data show that TMP has good and fast penetration properties into the CNS and is therefore a valuable ligand for precisely controlling protein expression in the CNS in rodents.