publications
2023
- Sci. Adv.Cortical circuits modulate mouse social vocalizationsBenjamin Gan-Or, and Michael LondonScience Advances, Sep 2023
Vocalizations provide a means of communication with high fidelity and information rate for many species. Male mice emit ultrasonic vocalizations (USVs) during female courtship. Diencephalon and brainstem neural circuits have been shown to control the production of USVs, however, the role of cortical circuits in this process is debatable. We show that male mice produced USVs following intracortical microstimulation (ICMS) in a specific location of their anterior cingulate cortex (ACC). Moreover, ACC Ca2+-imaging showed an increase in Ca2+ dynamics preceding USV initiation. Optogenetically suppressing ACC activity caused mice to emit fewer USVs during courtship. Neuropixel electrophysiological recordings in head-restrained male mice indicated a differential increase in neural activity in response to female social exposure (SE). The firing rate in SE trials where USVs were emitted was significantly higher when compared to SE leading to silence. Taken together, these results indicate that the ACC is a key node in the neuronal circuits controlling USV production.
2020
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Temporal structure of mouse courtship vocalizations facilitates syllable labelingS Hertz, B Weiner, N Peretz, and M LondonCommunications Biology, Jun 2020Mice emit sequences of ultrasonic vocalizations (USVs) but little is known about the rules governing their temporal order and no consensus exists on the classification of USVs into syllables. To address these questions, we recorded USVs during male-female courtship and found a significant temporal structure. We labeled USVs using three popular algorithms and found that there was no one-to-one relationships between their labels. As label assignment affects the high order temporal structure, we developed the Syntax Information Score (based on information theory) to rank labeling algorithms based on how well they predict the next syllable in a sequence. Finally, we derived a novel algorithm (Syntax Information Maximization) that utilizes sequence statistics to improve the clustering of individual USVs with respect to the underlying sequence structure. Improvement in USV classification is crucial for understanding neural control of vocalization. We demonstrate that USV syntax holds valuable information towards achieving this goal.
2018
- Cell Rep.Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In VivoC Labarrera, Y Deitcher, A Dudai, B Weiner, A Kaduri-Amichai, N Zylbermann, and M LondonCell Reports, Apr 2018
The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the α2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca2+ events in the tuft and lowers the threshold for dendritic Ca2+ spikes. We further show that these effects are likely to be mediated by the dendritic current Ih. Modulation of Ih in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs.
2016
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Social Ultrasonic Vocalization in Awake Head-Restrained MouseB Weiner, S Hertz, N Perets, and M LondonFrontiers in Behavioral Neuroscience, Dec 2016Numerous animal species emit vocalizations in response to various social stimuli. The neural basis of vocal communication has been investigated in monkeys, songbirds, rats, bats, and invertebrates resulting in deep insights into motor control, neural coding, and learning. Mice, which recently became very popular as a model system for mammalian neuroscience, also utilize ultrasonic vocalizations (USVs) during mating behavior. However, our knowledge is lacking of both the behavior and its underlying neural mechanism. We developed a novel method for head-restrained male mice (HRMM) to interact with non-restrained female mice (NRFM) and show that mice can emit USVs in this context. We first recorded USVs in a free arena with non-restrained male mice (NRMM) and NRFM. Of the NRMM, which vocalized in the free arena, the majority could be habituated to also vocalize while head-restrained but only when a female mouse was present in proximity. The USVs emitted by HRMM are similar to the USVs of NRMM in the presence of a female mouse in their spectral structure, inter-syllable interval distribution, and USV sequence length, and therefore are interpreted as social USVs. By analyzing the vocalizations of NRMM, we established criteria to predict which individuals are likely to vocalize while head fixed based on the USV rate and average syllable duration. To characterize the USVs emitted by HRMM, we analyzed the syllable composition of HRMM and NRMM and found that USVs emitted by HRMM have a higher proportion of USVs with complex spectral representation, supporting previous studies showing that mice social USVs are context dependent. Our results suggest a way to study the neural mechanisms of production and control of social vocalization in mice using advanced methods requiring head fixation.
2014
- Cereb. CortexImpaired Development and Competitive Refinement of the Cortical Frequency Map in Tumor Necrosis Factor-α-Deficient MiceCerebral Cortex, Jul 2014
Early experience shapes sensory representations in a critical period of heightened plasticity. This adaptive process is thought to involve both Hebbian and homeostatic synaptic plasticity. Although Hebbian plasticity has been investigated as a mechanism for cortical map reorganization, less is known about the contribution of homeostatic plasticity. We investigated the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in the primary auditory cortex using the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity. Our results indicate that these mice develop weaker tonal responses and incomplete frequency representations. Rearing in a single-frequency revealed a normal expansion of cortical representations in KO mice. However, TNF-α KOs lacked homeostatic adjustments of cortical responses following exposure to multiple frequencies. Specifically, while this sensory over-stimulation resulted in competitive refinement of frequency tuning in wild-type controls, it broadened frequency tuning in TNF-α KOs. Our results suggest that homeostatic plasticity plays an important role in gain control and competitive interaction in sensory cortical development.
2011
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Homeostatic plasticity drives tinnitus perception in an animal modelProceedings of the National Academy of Sciences, Sep 2011Hearing loss often results in tinnitus and auditory cortical map changes, leading to the prevailing view that the phantom perception is associated with cortical reorganization. However, we show here that tinnitus is mediated by a cortical area lacking map reorganization. High-frequency hearing loss results in two distinct cortical regions: a sensory-deprived region characterized by a decrease in inhibitory synaptic transmission and a normal hearing region showing increases in inhibitory and excitatory transmission and map reorganization. Hearing-lesioned animals displayed tinnitus with a pitch in the hearing loss range. Furthermore, drugs that enhance inhibition, but not those that reduce excitation, reversibly eliminated the tinnitus behavior. These results suggest that sensory deprivation-induced homeostatic down-regulation of inhibitory synapses may contribute to tinnitus perception. Enhancing sensory input through map reorganization may plausibly alleviate phantom sensation.