Emily Prevost
@emilyprevost.bsky.social
Behavioral Neuroscience PhD candidate in the Root Lab at the University of Colorado Boulder. Cellular heterogeneity in motivational systems. Expected graduation spring 2026. Gardener, skier, dog mom, and backyard chicken farmer. she/her
Want to thank all who helped bring this project to light! @anniely.bsky.social , @ampolter.bsky.social , @neuronroot.bsky.social and all those who aren't on Bluesky
February 27, 2025 at 7:25 PM
Want to thank all who helped bring this project to light! @anniely.bsky.social , @ampolter.bsky.social , @neuronroot.bsky.social and all those who aren't on Bluesky
Altogether, we conclude that the signaling patterns and behavioral functions of VTA dopamine neurons depend on whether they co-transmit glutamate or release dopamine alone. Distinct glu and DA subpops—and individual NTs in co-transmitting neurons—contribute differentially to motivated behaviors 21/n
February 27, 2025 at 7:25 PM
Altogether, we conclude that the signaling patterns and behavioral functions of VTA dopamine neurons depend on whether they co-transmit glutamate or release dopamine alone. Distinct glu and DA subpops—and individual NTs in co-transmitting neurons—contribute differentially to motivated behaviors 21/n
Finally, Zachary Kilpatrick expanded a classic neural circuit model of temporal-difference learning to account for glu-DA neurons, as well as the individual contributions of glutamate and dopamine from glu-DA and DA-only neurons. The model recapitulated some of our key behavioral results. 20/n
February 27, 2025 at 7:25 PM
Finally, Zachary Kilpatrick expanded a classic neural circuit model of temporal-difference learning to account for glu-DA neurons, as well as the individual contributions of glutamate and dopamine from glu-DA and DA-only neurons. The model recapitulated some of our key behavioral results. 20/n
…But blocking glutamate release did not cause gross motor deficits which might explain the differences, nor impair escape responses to a simulated predator. We concluded that blocking glutamate release impairs reward- and exploration-related vigor without affecting aversion-related vigor. 19/n
February 27, 2025 at 7:25 PM
…But blocking glutamate release did not cause gross motor deficits which might explain the differences, nor impair escape responses to a simulated predator. We concluded that blocking glutamate release impairs reward- and exploration-related vigor without affecting aversion-related vigor. 19/n
Blocking glutamate release did not impact the acquisition of reward learning or fear learning/extinction. But it slowed reward retrieval latency and enhanced reward extinction, and suppressed exploratory behavior in an open field… 18/n
February 27, 2025 at 7:25 PM
Blocking glutamate release did not impact the acquisition of reward learning or fear learning/extinction. But it slowed reward retrieval latency and enhanced reward extinction, and suppressed exploratory behavior in an open field… 18/n
Knocking down TH (to block DA synthesis) didn’t impact acquisition of reward learning. But mice had deficits when learning about less-rewarding (reward CS-, reward extinction) or aversive (shock CS+) associations. 17/n
February 27, 2025 at 7:25 PM
Knocking down TH (to block DA synthesis) didn’t impact acquisition of reward learning. But mice had deficits when learning about less-rewarding (reward CS-, reward extinction) or aversive (shock CS+) associations. 17/n
We zoomed in on glu-DA co-transmitting neurons and identified distinct functional roles for glu release and DA release in motivated behaviors. Using recombinase-dependent shRNA vectors, we blocked molecules necessary for DA synthesis (in glu neurons) or vesicular glu release (in DA neurons) 16/n
February 27, 2025 at 7:25 PM
We zoomed in on glu-DA co-transmitting neurons and identified distinct functional roles for glu release and DA release in motivated behaviors. Using recombinase-dependent shRNA vectors, we blocked molecules necessary for DA synthesis (in glu neurons) or vesicular glu release (in DA neurons) 16/n
Anatomically, we also observed (as others have before) that glu-DA neurons heavily innervate NAcc medial shell, with some innervation in medial core. DA-only neurons heavily innervate NAcc core with some innervation in ventral and lateral shell. 15/n
February 27, 2025 at 7:25 PM
Anatomically, we also observed (as others have before) that glu-DA neurons heavily innervate NAcc medial shell, with some innervation in medial core. DA-only neurons heavily innervate NAcc core with some innervation in ventral and lateral shell. 15/n
We used ChRmine & GRABDA to measure opto-elicited NAcc DA release from VTA glu-DA or DA-only terminals. Axonal stim in both subpops increased DA release. Glu-DA axons were more sensitive to longer pulse trains in phasic magnitude. DA-only were more sensitive to longer trains in tonic duration 14/n
February 27, 2025 at 7:25 PM
We used ChRmine & GRABDA to measure opto-elicited NAcc DA release from VTA glu-DA or DA-only terminals. Axonal stim in both subpops increased DA release. Glu-DA axons were more sensitive to longer pulse trains in phasic magnitude. DA-only were more sensitive to longer trains in tonic duration 14/n
In sum, glu-DA neurons were activated in both rewarding and aversive contexts, but DA-only neurons had bidirectional activity in reward vs aversion. Examining all DA neurons together obscures the dissociable activity of subpops. Glu-only neurons are distinct from previously studied VTA subpops. 13/n
February 27, 2025 at 7:25 PM
In sum, glu-DA neurons were activated in both rewarding and aversive contexts, but DA-only neurons had bidirectional activity in reward vs aversion. Examining all DA neurons together obscures the dissociable activity of subpops. Glu-only neurons are distinct from previously studied VTA subpops. 13/n
Importantly, in the nonselective population of all dopamine neurons together, we saw intermediate results between glu-DA and DA-only subpops. This is best exemplified in RPE signaling as well as shock and shock-predictive cue signaling (see previous posts). 12/n
February 27, 2025 at 7:25 PM
Importantly, in the nonselective population of all dopamine neurons together, we saw intermediate results between glu-DA and DA-only subpops. This is best exemplified in RPE signaling as well as shock and shock-predictive cue signaling (see previous posts). 12/n
Differences in signaling dynamics were starker in an aversive context. Glu-DA and glu-only neurons were activated to shock and the shock-predictive cue—glu-DA neurons strongly so. When measuring the minimum GCaMP value, we saw that DA-only neurons were suppressed at shock and cue. 11/n
February 27, 2025 at 7:25 PM
Differences in signaling dynamics were starker in an aversive context. Glu-DA and glu-only neurons were activated to shock and the shock-predictive cue—glu-DA neurons strongly so. When measuring the minimum GCaMP value, we saw that DA-only neurons were suppressed at shock and cue. 11/n
Considering both RPE signaling and behavior-dependent signaling during the non-predictive cue, it appears that DA-only neurons suppress their activity when the animal recognizes that reward is not forthcoming. This was not observed in glu-DA or glu-only neurons. 10/n
February 27, 2025 at 7:25 PM
Considering both RPE signaling and behavior-dependent signaling during the non-predictive cue, it appears that DA-only neurons suppress their activity when the animal recognizes that reward is not forthcoming. This was not observed in glu-DA or glu-only neurons. 10/n
Interestingly, DA-only neurons responded to the neutral cue (CS-) depending on the mouse’s behavior. When the mouse correctly avoided the port, activity decreased at the cue. But when the mouse incorrectly entered the port, activity decreased at the time reward “would” have come on a CS+ trial. 9/n
February 27, 2025 at 7:25 PM
Interestingly, DA-only neurons responded to the neutral cue (CS-) depending on the mouse’s behavior. When the mouse correctly avoided the port, activity decreased at the cue. But when the mouse incorrectly entered the port, activity decreased at the time reward “would” have come on a CS+ trial. 9/n
When an expected reward was omitted (reward prediction error), sustained activity of glu-DA neurons prevented a suppression below baseline, while transient activity of DA-only and glu-only allowed RPE signaling. This is the first RPE signaling identified in a VTA glutamate subpopulation. 8/n
February 27, 2025 at 7:25 PM
When an expected reward was omitted (reward prediction error), sustained activity of glu-DA neurons prevented a suppression below baseline, while transient activity of DA-only and glu-only allowed RPE signaling. This is the first RPE signaling identified in a VTA glutamate subpopulation. 8/n
In Pavlovian reward, all subpops were activated at reward and reward-predictive cue. But glu-DA neurons exhibited sustained activation between cue and reward peaks, while DA-only and glu-only exhibited transient activation in which activity dropped toward baseline between cue and reward peaks. 7/n
February 27, 2025 at 7:25 PM
In Pavlovian reward, all subpops were activated at reward and reward-predictive cue. But glu-DA neurons exhibited sustained activation between cue and reward peaks, while DA-only and glu-only exhibited transient activation in which activity dropped toward baseline between cue and reward peaks. 7/n
In vivo, we found that these subpops are dissociable in GCaMP signaling dynamics related to rewarding and aversive cues and outcomes: 6/n
February 27, 2025 at 7:25 PM
In vivo, we found that these subpops are dissociable in GCaMP signaling dynamics related to rewarding and aversive cues and outcomes: 6/n
The incredible @ampolter.bsky.social and Kailyn Price demonstrated that these subpops are electrophysiologically distinct. Some highlights: a subset of glutamate-only neurons exhibited Ih and D2 sensitivity; glutamate-dopamine neurons largely lacked Ih. 5/n
February 27, 2025 at 7:25 PM
The incredible @ampolter.bsky.social and Kailyn Price demonstrated that these subpops are electrophysiologically distinct. Some highlights: a subset of glutamate-only neurons exhibited Ih and D2 sensitivity; glutamate-dopamine neurons largely lacked Ih. 5/n
Additionally, we used a subtractive genetic strategy to target (for the first time) neurons that do not release dopamine and do not release GABA, which in the VTA selects for neurons that release glutamate alone. Our cellular targeting strategy is summarized here. 4/n
February 27, 2025 at 7:25 PM
Additionally, we used a subtractive genetic strategy to target (for the first time) neurons that do not release dopamine and do not release GABA, which in the VTA selects for neurons that release glutamate alone. Our cellular targeting strategy is summarized here. 4/n
Using INTRSECTional genetics, we isolated VTA populations that co-transmit dopamine and glutamate or release dopamine alone (without glutamate). We compared this to current standard, which is to examine all dopamine neurons together regardless of co-transmission. See next for a visual summary. 3/n
February 27, 2025 at 7:25 PM
Using INTRSECTional genetics, we isolated VTA populations that co-transmit dopamine and glutamate or release dopamine alone (without glutamate). We compared this to current standard, which is to examine all dopamine neurons together regardless of co-transmission. See next for a visual summary. 3/n
Despite well-known molecular heterogeneity in VTA dopamine neurons (esp. glutamate co-transmission), hypotheses of VTA dopamine function presume a homogenous influence on behavior. We examined the functional consequences of heterogeneity in VTA dopamine and glutamate subpopulations 2/n
February 27, 2025 at 7:25 PM
Despite well-known molecular heterogeneity in VTA dopamine neurons (esp. glutamate co-transmission), hypotheses of VTA dopamine function presume a homogenous influence on behavior. We examined the functional consequences of heterogeneity in VTA dopamine and glutamate subpopulations 2/n