Lior Cohen

Multisensory Integration of Natural Odors and Sounds in the Auditory Cortex

VIDEO ABSTRACTnMotherhood is associated with different forms of physiological alterations including transient hormonal changes and brain plasticity. The underlying impact of these changes on the emergence of maternal behaviors and sensory processing within the mothers brain are largely unknown. By using inxa0vivo cell-attached recordings in the primary auditory cortex of female mice, we discovered that exposure to pups body odor reshapes neuronal responses to pure tones and natural auditory stimuli. This olfactory-auditory interaction appeared naturally in lactating mothers shortly after parturition and was long lasting. Naive virgins that had experience with the pups also showed an appearance of olfactory-auditory integration in A1, suggesting that multisensory integration may be experience dependent. Neurons from lactating mothers were more sensitive to sounds as compared to those from experienced mice, independent of the odor effects. These uni- and multisensory cortical changes may facilitate the detection and discrimination of pup distress calls and strengthen the bond between mothers and their neonates.

Molecular Requirements for Recognition of Brain Voltage-gated Sodium Channels by Scorpion α-Toxins

The scorpion α-toxin Lqh2 (from Leiurus quinquestriatus hebraeus) is active at various mammalian voltage-gated sodium channels (Navs) and is inactive at insect Navs. To resolve the molecular basis of this preference we used the following strategy: 1) Lqh2 was expressed in recombinant form and key residues important for activity at the rat brain channel rNav1.2a were identified by mutagenesis. These residues form a bipartite functional surface made of a conserved “core domain” (residues of the loops connecting the secondary structure elements of the molecule core), and a variable “NC domain” (five-residue turn and the C-tail) as was reported for other scorpion α-toxins. 2) The functional role of the two domains was validated by their stepwise construction on the similar scaffold of the anti-insect toxin LqhαIT. Analysis of the activity of the intermediate constructs highlighted the critical role of Phe15 of the core domain in toxin potency at rNav1.2a, and has suggested that the shape of the NC-domain is important for toxin efficacy. 3) Based on these findings and by comparison with other scorpion α-toxins we were able to eliminate the activity of Lqh2 at rNav1.4 (skeletal muscle), hNav1.5 (cardiac), and rNav1.6 channels, with no hindrance of its activity at Nav1.1–1.3. These results suggest that by employing a similar approach the design of further target-selective sodium channel modifiers is imminent.

Plasticity during motherhood: changes in excitatory and inhibitory layer 2/3 neurons in auditory cortex.

Maternal behavior can be triggered by auditory and olfactory cues originating from the newborn. Here we report how the transition to motherhood affects excitatory and inhibitory neurons in layer 2/3 (L2/3) of the mouse primary auditory cortex. We used in vivo two-photon targeted cell-attached recording to compare the response properties of parvalbumin-expressing neurons (PVNs) and pyramidal glutamatergic neurons (PyrNs). The transition to motherhood shifts the average best frequency of PVNs to higher frequency by a full octave, with no significant effect on average best frequency of PyrNs. The presence of pup odors significantly reduced the spontaneous and evoked activity of PVN. This reduction of feedforward inhibition coincides with a complimentary increase in spontaneous and evoked activity of PyrNs. The selective shift of PVN frequency tuning should render pup odor-induced disinhibition more effective for high-frequency stimuli, such as ultrasonic vocalizations. Indeed, pup odors increased neuronal responses of PyrNs to pup ultrasonic vocalizations. We conclude that plasticity in the mothers is mediated, at least in part, via modulation of the feedforward inhibition circuitry in the auditory cortex.

Elevated Correlations in Neuronal Ensembles of Mouse Auditory Cortex Following Parturition

The auditory cortex is malleable by experience. Previous studies of auditory plasticity have described experience-dependent changes in response profiles of single neurons or changes in global tonotopic organization. However, experience-dependent changes in the dynamics of local neural populations have remained unexplored. In this study, we examined the influence of a dramatic yet natural experience in the life of female mice, giving birth and becoming a mother on single neurons and neuronal ensembles in the primary auditory cortex (A1). Using in vivo two-photon calcium imaging and electrophysiological recordings from layer 2/3 in A1 of mothers and age-matched virgin mice, we monitored changes in the responses to a set of artificial and natural sounds. Population dynamics underwent large changes as measured by pairwise and higher-order correlations, with noise correlations increasing as much as twofold in lactating mothers. Concomitantly, changes in response properties of single neurons were modest and selective. Remarkably, despite the large changes in correlations, information about stimulus identity remained essentially the same in the two groups. Our results demonstrate changes in the correlation structure of neuronal activity as a result of a natural life event.

Time-lapse electrical recordings of single neurons from the mouse neocortex

The ability of the brain to adapt to environmental demands implies that neurons can change throughout life. The extent to which single neurons actually change remains largely unstudied, however. To evaluate how functional properties of single neurons change over time, we devised a way to perform in vivo time-lapse electrophysiological recordings from the exact same neuron. We monitored the contralateral and ipsilateral sensory-evoked spiking activity of individual L2/3 neurons from the somatosensory cortex of mice. At the end of the first recording session, we electroporated the neuron with a DNA plasmid to drive GFP expression. Then, 2 wk later, we visually guided a recording electrode in vivo to the GFP-expressing neuron for the second time. We found that contralateral and ipsilateral evoked responses (i.e., probability to respond, latency, and preference), and spontaneous activity of individual L2/3 pyramidal neurons are stable under control conditions, but that this stability could be rapidly disrupted. Contralateral whisker deprivation induced robust changes in sensory-evoked response profiles of single neurons. Our experiments provide a framework for studying the stability and plasticity of single neurons over long time scales using electrophysiology.

Demonstration of a quantum error correction for enhanced sensitivity of photonic measurements

The sensitivity of classical and quantum sensing is impaired in a noisy environment. Thus, one of the main challenges facing sensing protocols is to reduce the noise while preserving the signal. State of the art quantum sensing protocols that rely on dynamical decoupling achieve this goal under the restriction of long noise correlation times. We implement a proof-of-principle experiment of a protocol to recover sensitivity by using an error correction for photonic systems that does not have this restriction. The protocol uses a protected entangled qubit to correct a single error. Our results show a recovery of about 87% of the sensitivity, independent of the noise rate.

Direct observation of the degree of correlations using photon-number-resolving detectors

Optical parametric down-conversion is a common source for the generation of non-classical correlated photonic states. Using a parametric down-conversion source and photon-number resolving detectors, we measure the two-mode photon-number distribution of up to 10 photons. By changing the heralded collection efficiency, we control the level of correlations between the two modes. Clear evidence for photon-number correlations are presented despite detector imperfections such as low detection efficiency and other distorting effects. Two criteria, derived directly from the raw data, are shown to be good measures for the degree of correlation. Additionally, using a fitting technique, we find a connection between the measured photon-number distribution and the degree of correlation of the reconstructed original two-mode state. These observations are only possible as a result of the detection of high photon number events.

A pilot randomized clinical trial of cognitive behavioral therapy versus attentional bias modification for social anxiety disorder: An examination of outcomes and theory-based mechanisms

No studies have compared face-to-face cognitive-behavioral therapy (CBT) and attention bias modification (ABM) for social anxiety disorder (SAD) and their purported mechanisms. We asked: 1) Is CBT more effective than ABM? and 2) Are changes in attentional biases and cognitions temporally related to symptom change? Forty-three patients were randomly assigned to 8 sessions of ABM or up to 20 sessions of individual CBT. Intent-to-treat results revealed that CBT was superior to ABM in response rates and on symptom measures at endpoint, but not on other measures. No differences were found on measures in rates of change between CBT and ABM. Frequency of negative cognitions changed in both groups and negative beliefs changed only in CBT. Attentional bias did not change in either group. Cognitive changes bidirectionally correlated with symptom change in cross-lagged analyses in CBT, but not in ABM, suggesting a reciprocal relationship. Trial-level bias away from negative faces was simultaneously related to symptom change in ABM only. Results suggest that CBT is superior to ABM when administered at their typical doses, but raise questions given the similar rates of change. In addition, results support theories of cognitive change and raise questions about changes in attentional biases in CBT.

Low intensity LiDAR using compressed sensing and a photon number resolving detector

LiDAR (laser based radar) systems are a major part of many new real-world interactive systems, one of the most notable being autonomous cars. The current market LiDAR systems are limited by detector sensitivity: when output power is at eye-safe levels, the range is limited. Long range operation also slows image acquisition as ight-time increases. We present an approach that combines a high sensitivity photon number resolving diode with machine learning and a micro-mechanical digital mirror device to achieve safe and fast long range 3D scanning.

Positive Emotions and Social Anxiety: The Unique Role of Pride

Social anxiety is correlated with diminished global positive affect (PA). However, it is not clear from the data whether this relationship is due to global PA, or to specific emotions such as joy or pride. We hypothesized that pride will account for most of the relationship between social anxiety and PA after controlling for depression. Results of Study 1 (Nu2009=u2009352) supported the hypothesis that when pride and PA were in the same model, only pride was significantly related to social anxiety. The same pattern was found when pride and joy were in the same model. When multiple facets of positive emotions (pride, love, joy, contentment, amusement, awe and compassion) were in the same model, only pride and love were significantly related to social anxiety. Results of Study 2 (Nu2009=u2009288) replicated the findings that only pride was significantly related to social anxiety, but counter to our hypothesis, revealed that pride experience was significantly related to social anxiety more than reported expressions of pride. Study 3 extended these findings to a clinical, treatment seeking sample of 23 patients diagnosed with generalized social anxiety disorder and 35 low-anxious controls. When predicting group (patients vs. non-patient) by pride and PA, only pride was a significant predictor. Pride continued to be a predictor when controlling for either fear of positive or negative evaluation. Thus, all three studies demonstrated the importance of the specific experience of pride in its relationship to social anxiety.