New Pre-Print: Monosynaptic inputs to ventral tegmental area glutamate and GABA co- transmitting neurons

Congratulations to Emily Prevost and team on their pre-print Monosynaptic inputs to ventral tegmental area glutamate and GABA co-transmitting neurons. This work has been ongoing since we started the lab in 2018, which led us to develop SHARCQ for use here.

While the overall circuits of GABA-releasing or glutamate-releasing VTA neurons have been identified, the circuits of neurons that co-transmit glutamate and GABA are unknown. We used INTRSECT vectors, rabies tracing, and SHARCQ to identify the brainwide inputs to these co-transmitting neurons. Large numbers of inputs came from lateral hypothalamus and superior colliculus while the most dense inputs came from lateral habenula, dorsal raphe, and locally in the VTA. We hypothesized most inputs were glutamatergic and indeed found that lateral hypothalamus glutamate neurons as well as superior colliculus glutamate neurons functional activate VTA glutamate and GABA co-transmitting neurons. Activation of each neuron resulted in different behaviors related to threat interpretation but these behaviors did not correlate with VTA activity. We hypothesize that VTA glutamate and GABA co-transmitting neurons receive a general signal of threat via these pathways that does not involve the movements underlying the reaction to those threats. Finally, we supported that these neurons act as outcome detectors and the identified circuits here may be a mechanism by which they integrate information related to the detection and processing of motivationally-salient outcomes.

Check out the paper here

New Pre-Print: BNST GABA neurons are necessary for changes in foraging behavior following an innate threat

Congratulations to Annie Ly and team for their manuscript investigating the role of BNST GABA neurons in changes in foraging behavior in response to robotic or innate threat.

Annie adapted a robotic threat foraging paradigm from rats to mice. After that, she introduced a robotic threat or live predator threat while BNST GABA neurons were inhibited. Then she examined how these mice foraged in the subsequent absence of threat. Both threats impeded ongoing foraging. However, live predator threat impeded foraging in the subsequent absence of threat more than the robotic threat. Further, the changes in foraging behavior were blocked by previous inhibition of BNST GABA neurons during live predator threat, but not robotic threat. These results suggest BNST GABA neurons play a role in developing a hypervigilant state in response to a previous highly threatening situation.

See the pre-print here, now in peer review.

Ventral tegmental area glutamate neurons mediate nonassociative consequences of stress -- now published in Molecular Psychiatry

Congrats to Dillon McGovern, Mike Baratta, and team on the publication of our first collaboration on stress research! A lot more research has occurred since the original submission shown in our preprint at biorxiv.

Some highlights:
Behaviorally: Male and female mice show the effects uncontrollable stress differently. Males show reduced sociability and enhanced fear while females do not after stress. Females show reduced general exploratory behavior under mild threat (bright light) after stress. Male stress effects are dependent on the controllability of stress. Female mice show some effects dependent or independent on controllability.

Neurally: VTA glutamate neurons are required for the consequences of uncontrollable stress in both male and female mice. VTA glutamate neurons are activated by controllable and uncontrollable stress suggesting they do not discriminate the loss of control over stress (we’re working on where these neurons are though!). Genetically-distinct subtypes of VTA glutamate neurons are all activated by stress, but those that co-transmit glutamate and GABA are most activated. Lateral habenula neurons that receive synapses from VTA glutamate neurons are activated by stress (which we previously found were mostly from glutamate and GABA co-transmitting neurons), suggesting a cell-type specific pathway involved in the consequences of stress.

Check out the publication online ahead of print here

Root lab at SfN

Come check out the latest research from our group:
Emily Prevost on Sunday afternoon Nov 13 at 225.21 is presenting Brainwide tracing of monosynaptic inputs to ventral tegmental area glutamate-GABA co-transmitting neurons

Dillon McGovern on Monday afternoon Nov 14 at 398.08 is presenting Ventral tegmental area glutamate cell types differentially signal reward value

Annie Ly on Wednesday morning Nov 16 at 646.07 is presenting Bnst circuitry in stress-induced changes on exploratory behavior

Former lab PRA Connor McNulty is presenting Tuesday morning at 479.09 Behavioral control over stress recruits a distinct circuit in females

Collaborations with the Bob Spencer lab are by Will Stritzel: Nighttime red light sensitivity in laboratory rodents: suprachiasmatic nucleus activation, melatonin suppression, and phase shifted wheel running
and by Helen Strnad: Sleep- and circadian-related calcium activity and diurnal clock gene expression in serotonergic neurons of the adult rat dorsal raphe nucleus