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Loveless, M. C.

Publications and source records attributed to Loveless, M. C..

3 recordsLinked to original sources

Multidimensional control of ingestive behavior by lateral hypothalamic neurotensin neurons

Consumption of food and water is regulated by interactions between neural circuits that govern motivational drive states, arousal, motor activity, and reward signaling, among other factors. Neurons in the lateral hypothalamus that express the neuropeptide neurotensin (LH-Nts neurons) are known to influence many of these elements, but their precise role in regulating specific aspects of ingestive behavior remains unclear. Utilizing a tightly controlled head-fixed task, we find that LH-Nts neurons strongly encode the rate of licking for water and sweet solutions, with weaker modulation of activity by solution identity and restriction state. Silencing LH-Nts neurons reduces water intake but has little direct effect on hunger or satiety. Instead, we find that these neurons impact multiple underlying behavioral components necessary for food consumption, including arousal and engagement with a novel food source, and also influence thermoregulation and metabolism. Together, these data establish tonic activity of LH-Nts neurons as a critical signal supporting exploration and volitional movement, while also delineating a role for these neurons in driving active consumption, particularly of water. Furthermore, quantitative projection mapping revealed widespread innervation of structures linked to thirst, arousal, reward, metabolism, and facial motor control, suggesting that these neurons play an important role coordinating neural circuits governing multiple different aspects of ingestion.

neuroscience↗

Periaqueductal gray neurotensin neurons drive simultaneousthreat response and reinforcement

The periaqueductal gray (PAG) is a midbrain structure known to influence responses to both threat and reward. The PAG sends projections to the ventral tegmental area (VTA), a region critical for regulating motivated behavior via dopamine release. We previously identified a population of VTA-projecting PAG neurons that express the peptide neurotensin (Nts), a potent dopamine neuron activator. Here we find that PAG-Nts neurons co-release glutamate and Nts in the VTA to drive dopamine neuron activation. These neurons are activated by threats and threat-predictive cues and are inhibited by entry into a shelter and during reward consumption. Optogenetic stimulation elicits a robust threat response, including freezing and tail rattle, but remarkably can also drive intracranial self-stimulation. This operant reinforcement behavior is dopamine dependent while the threat response is not. Together, these results identify a dual-output circuit that engages the dopamine system, likely to increase the salience of environmental stimuli, while simultaneously driving specific threat response behaviors.

neuroscience↗

Opto-seq reveals input-specific immediate early gene induction in ventral tegmental area cell types

The ventral tegmental area (VTA) is a critical node in circuits governing motivated behavior and is home to diverse populations of neurons that release dopamine, GABA, glutamate, or combinations of these neurotransmitters. The VTA receives inputs from many brain regions, but a comprehensive understanding of input-specific activation of VTA neuronal subpopulations is lacking. To address this, we combined optogenetic stimulation of select VTA inputs with single-nucleus RNA sequencing (snRNAseq) and highly multiplexed in situ hybridization to identify distinct neuronal clusters and characterize their spatial distribution and activation patterns. Quantification of immediate early gene (IEG) expression revealed that different inputs activated select VTA subpopulations, which demonstrated cell-type specific IEG programs. Within dopaminergic subpopulations IEG induction levels correlated with differential expression of ion channel genes. This new transcriptomics-guided circuit analysis reveals the diversity of VTA activation driven by distinct inputs and provides a resource for future analysis of VTA cell types.

neuroscience↗