Biology subjects

Calva, C. B.

Publications and source records attributed to Calva, C. B..

3 recordsLinked to original sources

bioRxiv2026

Supramammillary projections to the lateral preoptic area drive dopamine release and active behavior

The supramammillary nucleus (SuM) is known to promote active, approach-oriented behaviors by engaging ventral tegmental area (VTA) dopamine neurons projecting to the nucleus accumbens (NAc), primarily via a glutamatergic SuM[->]medial septum (MS) pathway. However, the role of other SuM projections in this process remains unclear. Here we combined anatomical tracing, fiber photometry, chemogenetic, and optogenetic approaches to investigate the SuM[->]lateral preoptic area (LPO) pathway. We found that SuM[->]LPO neurons possess extensive collateral projections and are inhibited during consummatory behavior but activated by aversive and unexpected stimuli. Chemogenetic activation of these neurons reduced water intake and immobility during stress, while inhibition enhanced the appetitive phase for ingestive behavior and fear-related immobility. Optogenetic stimulation of SuM[->]LPO terminals reinforced behavior and elicited dopamine release in the NAc. These findings identify the SuM[->]LPO pathway as a distinct circuit that, alongside the SuM[->]MS pathway, engages mesolimbic dopamine signaling to facilitate active behavioral responses to environmental challenges.

neuroscience↗

bioRxiv2020

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

How does the prefrontal cortex (PFC) regulate motivated behavior? Our experiments characterize the circuits of the PFC regulating motivation, reinforcement and dopamine activity, revealing a novel cortico-thalamic loop. The stimulation of medial PFC (mPFC) neurons activated many downstream regions, as shown by functional MRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. Reciprocal excitatory functional connectivity, as well as co-activation of the two regions, was found in human participants who watched reinforcing videos. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement and dopaminergic neuron activity.

neuroscience↗

bioRxiv2020

Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction

The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to illuminate how SuM neurons mediate such effects. The excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by the projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway is important in reinforcement and approach motivation and may play an important role in mood and substance-use disorders.

neuroscience↗