Biology subjects

Sciolino, N. R.

Publications and source records attributed to Sciolino, N. R..

7 recordsLinked to original sources

bioRxiv2026

Lateral hypothalamic GABAergic projections to the dorsal pons and lateral preoptic area in feeding, predation, and reinforcement

Lateral hypothalamic GABAergic (LHAGABA) neurons regulate arousal, feeding, and reward-related behaviors, but how their downstream projections coordinate motivated behaviors across domains remains incompletely defined. Our histological analyses revealed that LHAGABA fibers were distributed across the dorsal pons (DP) subregions, including the peri-locus coeruleus, laterodorsal tegmentum, and Barringtons nucleus, and extend throughout the lateral preoptic area (LPO), thereby refining existing anatomical descriptions. We then used optogenetics to systematically compare the effects of activating LHAGABA somata and their projections to the DP and LPO across assays of feeding, non-food-directed gnawing, predatory behavior, real-time place preference, and operant self-stimulation. In sated mice, optogenetic activation of LHAGABA somata or their terminals in the DP or LPO increased caloric food intake, whereas non-caloric cellulose intake was minimally affected during terminal stimulation. Across conditions, activation increased gnawing and shredding of non-food objects while reducing inactivity. In cricket hunting, stimulation increased cricket killing and consumption relative to controls. Similarly, all stimulation conditions supported positive-valence and reinforcement-related responding, as indicated by real-time place preference and operant self-stimulation. Together, these results provide new functional evidence that activation of LHAGABA somata and projections to both the DP and LPO recruit largely overlapping behavioral responses across feeding, non-food behavior, predatory hunting, and reinforcement-related assays. These findings support a distributed hypothalamic output architecture in which major ascending and descending LHAGABA pathways contribute to a shared motivational repertoire rather than wholly discrete behavioral functions.

neuroscience↗

bioRxiv2026

Locus coeruleus activation transforms cortical taste representations

Norepinephrine neurons in the locus coeruleus (LC) shape sensory responses across the brain, yet how LC activity reorganizes population representations of behaviorally relevant sensory attributes remains unclear. We addressed this question in the primary gustatory cortex (GC), a system largely unexplored in neuromodulation research and well-suited for linking sensory coding to affective value. Using miniscope calcium imaging in awake mice combined with optogenetic LC activation, we tested how phasic and tonic LC activity modulate GC encoding of three taste attributes: palatability, mixture ratio, and intensity. Phasic LC activation enhanced correlations between neuronal responses and tastant palatability and expanded the dynamic range of taste representations along a palatability-relevant axis. This expansion was driven primarily by an aversive shift in the representation of all tastants except sucrose, the most palatable stimulus. For mixture ratio and concentration, LC activation induced both stretching and rotation of attribute axes, potentially reflecting dependencies between these attributes and palatability. Analysis of LC-induced changes in neuronal tuning revealed that these population-level transformations likely arise from a combination of multiplicative gain modulation and flexible, tastant-specific changes in tuning. In contrast, tonic LC activation engaged fewer GC neurons and did not produce stretching along any attribute axis, demonstrating that LC effects on population coding depend on activation pattern. Together, these findings provide causal evidence that phasic LC activation reshapes GC population geometry to preferentially enhance palatability encoding, establishing a framework for understanding how neuromodulation may bias taste representations relevant to feeding behavior.

neuroscience↗

bioRxiv2023

Partial or complete loss of norepinephrine differentially alters contextual fear and catecholamine release dynamics in hippocampal CA1

Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Utilizing GRABNE and GRABDA sensors, in vivo fiber photometry, and two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis, we investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning. We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Partial loss of LC-NE synthesis reveals that NE release dynamics are modulated by sex. Moreover, we find that recall of recent fear memory is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, remote recall is compromised only by complete loss of LC-NE synthesis beginning prenatally. Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling.

neuroscience↗

bioRxiv2022

Integrity of the minor spliceosome in the developing mouse hypothalamus determines neuronal subtype composition regulating energy balance.

While gene regulatory networks underlying hypothalamic development are being characterized, minor intron splicing remains unexplored. Here, we used Nkx2.1-Cre to ablate Rnu11, encoding the minor spliceosome-specific U11 snRNA, in the progenitors of the ventral diencephalon (VD), to study minor intron splicing in hypothalamic development and control of energy balance in mice. Loss of U11 resulted in aberrant minor intron splicing, mitotic stalling, apoptosis, and altered neurogenesis. Mutant mice exhibited gross dysgenesis of hypothalamic architecture, while single-cell RNA sequencing (scRNAseq) revealed aberrant composition of neuronal subtypes implicated in feeding and energy balance. Mutant weanlings failed to thrive, followed by rapid weight gain, resulting in obesity. Assessment of energy imbalance and pair-feeding demonstrated that hyperphagia in adult mutants initiates weight gain, and is compounded by metabolic dysfunction, ultimately resulting in obesity. Our findings suggest a key role of minor intron splicing in the developmental patterning of hypothalamic neuronal subtypes underlying energy balance.

neuroscience↗

bioRxiv2021

Chemogenetic activation of Locus Coeruleus Noradrenergic Neurons Modulates the Default Mode Network

The default mode network (DMN) of the brain is involved in cognition, emotion regulation, impulsivity, and balancing between internally and externally focused states. DMN dysregulation has been implicated in several neurological and neuropsychiatric disorders. In this study, we used functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and spectral fiber-photometry to investigate the selective neuromodulatory effect of norepinephrine (NE)-releasing noradrenergic neurons in the locus coeruleus (LC) on the DMN in mice. Chemogenetic-induced tonic LC-NE activity decreased cerebral blood volume (CBV) and glucose uptake, and increased synchronous low frequency fMRI activity within the frontal cortices of the DMN. Fiber-photometry results corroborated these findings, showing that LC-NE activation induced NE release, enhanced calcium-weighted neuronal spiking, and reduced CBV in the anterior cingulate cortex. These data suggest that LC-NE alters conventional stimulus-evoked coupling between neuronal activity and CBV in the frontal DMN. We also demonstrated that chemogenetic activation of LC-NE neurons strengthened functional connectivity within the frontal DMN, and this effect was causally mediated by reduced modulatory inputs from retrosplenial and hippocampal regions to the association cortices of the DMN.

neuroscience↗

bioRxiv2019

A role for the locus coeruleus in the modulation of feeding

Recent data suggest that LC-NE neurons play a role in fear-induced suppression of feeding, but their endogenous activity in naturally behaving animals has not been explored. We found that endogenous activity of LC-NE neurons was enhanced during food approach and suppressed during food consumption, and that these food-evoked LC-NE responses were attenuated in sated mice. Interestingly, visual-evoked LC-NE activity was also attenuated in sated mice, demonstrating that internal satiety state modulates LC-NE encoding of multiple behavioral states. We also found that food intake could be attenuated by brief or longer durations of LC-NE activation. Lastly, we demonstrated that activation of LC neurons suppresses feeding and enhances avoidance and anxiety-like responding through a projection to the lateral hypothalamus. Collectively, our data suggest that LC-NE neurons modulate feeding by integrating both external cues (e.g., anxiogenic environmental cues) and internal drives (e.g., nutritional state).

neuroscience↗

bioRxiv2019

Elimination of galanin synthesis in noradrenergic neurons reduces galanin in select brain areas and promotes active coping behaviors

Accumulating evidence indicates that disruption of galanin signaling is associated with neuropsychiatric disease, but the precise functions of this neuropeptide remain largely unresolved due to lack of tools for experimentally disrupting its transmission in a cell type-specific manner. To examine the function of galanin in the noradrenergic system, we generated and crossed two novel knock-in mouse lines to create animals lacking galanin specifically in noradrenergic neurons (GalcKO-Dbh). We observed reduced levels of galanin peptide in pons, hippocampus, and prefrontal cortex of GalcKO-Dbh mice, indicating that noradrenergic neurons are a significant source of galanin to those brain regions, while midbrain and hypothalamic galanin levels were comparable to littermate controls. In these same brain regions, we observed no change in levels of norepinephrine or its major metabolite at baseline or after an acute stressor, suggesting that loss of galanin does not affect noradrenergic synthesis or turnover. GalcKO-Dbh mice had normal performance in tests of depression, learning, and motor-related behavior, but had an altered response in some anxiety-related tasks. Specifically, GalcKO-Dbh mice showed increased marble and shock probe burying and had a reduced latency to eat in a novel environment, indicative of a more proactive coping strategy. Together, these findings indicate that noradrenergic neurons provide a significant source of galanin to discrete brain areas, and noradrenergic-specific galanin opposes adaptive coping responses.

neuroscience↗