Biology subjects

Lischinsky, J. E.

Publications and source records attributed to Lischinsky, J. E..

4 recordsLinked to original sources

bioRxiv2026

Dopamine serves as an independent gain regulator to shape striatal control of movement

Dopamine (DA) drives locomotion by modulating striatal activity in the dorsolateral striatum (DLS). How DA regulates motor function on subsecond timescales remains poorly understood. To address this question, we performed spectrally resolved triple-color fiber photometry, allowing us to simultaneously monitor DA, glutamatergic inputs, and pathway-specific spiny projection neuron (SPN) activity in freely moving mice during spontaneous behaviors as measured by unsupervised behavior quantifications. We showed that DA dynamics were temporally distinct from spontaneous locomotor kinematics or behavioral states. Instead, peri-event DA levels predicted SPN input-output (I/O) efficacy, defined as SPN activity relative to glutamatergic input, with opposite relationships across pathways: higher DA predicted enhanced efficacy in direct-pathway SPNs but reduced efficacy in indirect-pathway SPNs. Paired with unsupervised behavior quantification, elevating extracellular DA with methylphenidate, a DA re-uptake inhibitor, shifted direct-pathway SPNs toward higher I/O gain and indirect-pathway SPNs toward lower neuronal activity outputs, while biasing behavior toward selected mobile and turning states. Reserpine administration, which mediates DA vesicular depletion, resulted in the opposite efficacy shifts and increased occupancy of immobile states. Together, these findings support that DA does not simply encode spontaneous movement, but acts as a pathway-specific gain controller that dynamically tunes the transformation of glutamatergic input into SPN output to bias locomotor-state transitions in vivo.

neuroscience↗

bioRxiv2023

Monitoring norepinephrine release in vivo using next-generation GRABNE sensors

Norepinephrine (NE) is an essential biogenic monoamine neurotransmitter, yet researches using prototype NE sensors were limited by their low sensitivities. Here, we developed next-generation versions of GPCR activation-based NE sensors (GRABNE2m and GRABNE2h) with a superior response, high sensitivity and selectivity to NE both in vitro and in vivo. Notably, these sensors can detect NE release triggered by either optogenetic or behavioral stimuli in freely moving mice, producing robust signals in the locus coeruleus and hypothalamus. With the development of a novel transgenic mouse line, we recorded both NE release and calcium dynamics with dual-color fiber photometry throughout the sleep-wake cycle; moreover, dual-color mesoscopic imaging revealed cell type-specific spatiotemporal dynamics of NE and calcium during sensory processing and locomotion. Thus, these new GRABNE sensors are valuable tools for monitoring the precise spatiotemporal release of NE in vivo, providing new insights into the physiological and pathophysiological roles of NE.

neuroscience↗

bioRxiv2023

Hardwired to attack: Transcriptionally defined amygdala subpopulations play distinct roles in innate social behaviors.

Social behaviors are innate and supported by dedicated neural circuits, but it remains unclear whether these circuits are developmentally hardwired or established through social experience. Here, we revealed distinct response patterns and functions in social behavior of medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages. MeA cells in male mice that express the transcription factor Foxp2 (MeAFoxp2) are specialized for processing male conspecific cues even before puberty and are essential for adult inter-male aggression. In contrast, MeA cells derived from the Dbx1-lineage (MeADbx1) respond broadly to social cues and are non-essential for male aggression. Furthermore, MeAFoxp2 and MeADbx1 cells show differential anatomical and functional connectivity. Altogether, our results support a developmentally hardwired aggression circuit at the level of the MeA and we propose a lineage-based circuit organization by which a cells embryonic transcription factor profile determines its social information representation and behavior relevance during adulthood. HighlightsO_LIMeAFoxp2 cells in male mice show highly specific responses to male conspecific cues and during attack while MeADbx1 cells are broadly tuned to social cues. C_LIO_LIThe male-specific response of MeAFoxp2 cells is present in naive adult males and adult social experience refines the response by increasing its trial-to-trial reliability and temporal precision. C_LIO_LIMeAFoxp2 cells show biased response to males even before puberty. C_LIO_LIActivation of MeAFoxp2, but not MeADbx1, cells promote inter-male aggression in naive male mice. C_LIO_LIInactivation of MeAFoxp2, but not MeADbx1, cells suppresses inter-male aggression. C_LIO_LIMeAFoxp2 and MeADbx1 cells show differential connectivity at both the input and output levels. C_LI

neuroscience↗

bioRxiv2023

Neural dynamics in the limbic system during male social behaviors

Sexual and aggressive behaviors are two evolutionarily conserved social behaviors vital for an animals survival and reproductive success. While an increasing number of brain regions in the limbic system have been identified as functionally relevant for these two types of behaviors, an understanding of how social cues are represented across brain regions and how social behaviors are generated via this network activity remains elusive. To gain a holistic view of the neural responses during social behaviors, we utilized multi-fiber photometry to simultaneously record Ca2+ signals of estrogen receptor alpha (Esr1)-expressing cells from 13 limbic brain regions in male mice during sexual and aggressive behaviors and compare the response magnitude and temporal patterns across regions. We find that conspecific sensory information, as well as social action initiation signals, are widely distributed in the limbic system and can be decoded from the network activity. Cross-region correlation analysis reveals striking increases in functional connectivity in the network during the action initiation phase of social behaviors whereas advanced copulation is accompanied by a "dissociated" network state. Based on the response patterns, we propose a mating-biased network (MBN) and an aggression-biased network (ABN) for mediating male sexual and aggressive behaviors, respectively.

neuroscience↗