Mission and Goals
The CCB Seed Grant is a pilot program by the Center on Compulsive Behaviors aimed at providing IRP postdoctoral fellows with an opportunity to move beyond Associate/Lead Associate Investigator roles to take on an official Principal Investigator (PI) role in a NIH grant.
The goal of the CCB Seed Grant program is in line with the CCB mission of creating a community where researchers across the preclinical-clinical divide discuss shared interests and develop joint projects. Thus, the application process for the CCB Seed Grant is highly interactive and collaborative and can serve as a stepping-stone towards the available extramural grants for IRP postdoctoral fellows (e.g., K99/R00).
The CCB Seed Grant offers up to $20,000 to two IRP postdoctoral fellows (at least one should be a CCB fellow/alumni) to carry out a collaborative project with protected research time.
Beginning in 2020, CCB Fellow alumni Dr. Valerie Darcey and Dr. Daria Piacentino conceptualized and spearheaded the development of the CCB Seed Grant, and led the initiative through its first funding cycles which fostered collaboration between CCB post-doctoral fellows.
Call for Applications
The 2023-2024 CCB Seed Grant cycle is closed for new applications. Sign up for the listserv to receive notifications about the next application cycle.
Award Recipients
Katherine Savell, PhD (NIDA) and Adam Caccavano, PhD (NICHD)
2022 - 2023
Project Title:
Transcriptional and functional characterization of interneuron subpopulations within macaque hippocampus and prefrontal cortex
Abstract:
Compulsive behaviors, including drug-seeking, can be broadly viewed as disorders of cognitive flexibility. Multiple brain regions are involved in compulsive drug-seeking, including the prefrontal cortex (PFC) and hippocampus (HPC). Notably, frontal cortex is particularly enlarged in the primate neocortex relative to other mammalian species2,3, suggesting to fully understand this behavior, it is necessary to expand beyond rodent models. Within the PFC, the ventromedial PFC (vmPFC, Brodmann Areas 25, 32) is ancestrally related to HPC4, while the granular dorsolateral PFC (dlPFC, Brodmann Area 46) has no rodent homologue5, representing a primate-specific innovation. This proposal will combine novel transcriptomic and viral tools in non-human primates (rhesus macaques) to characterize electrophysiologic and transcriptomic differences in distinct neuronal subpopulations within the anterior HPC, vmPFC, and dlPFC. Inhibitory interneurons coordinate rhythmic activity within and across brain regions. This proposal focuses on two populations, together comprising ~70% of neocortical interneurons: parvalbumin-(PV) and somatostatin-expressing (SST) cells6. In addition to critically regulating excitatory: inhibitory (E:I) balance in cortical microcircuits7,8, PV/SST cells within the PFC have robust control over reversal learning9-11, and within the HPC are suppressed by opioids12-14. The McBain lab has identified regional differences in the opioid-mediated suppression of PV/SST inhibition between HPC and cortical regions in rodents, macaques, and humans. There are also differences in opioid receptor expression in these cell populations across cortical regions in mice15-17. This proposal will build on these findings by exploring the vmPFC/dlPFC relative to anterior HPC and augment the electrophysiological experiments of the McBain Lab with novel transcriptomic tools available through the expertise of the Hope lab. Our overarching hypothesis is that PV and SST neurons have region-specific transcriptional and functional programs in the primate that give rise to differential microcircuit motifs and inhibitory control.
Renata Marchette, PhD (NIDA) and Peter Manza, PhD (NIAAA)
2022 - 2023
Project Title:
A neural circuit selective for fast drug reward
Abstract:
The faster an addictive drug enters the brain, the greater its rewarding effects1. Yet we lack basic knowledge about which circuits are sensitive to the speed at which a drug enters the brain. The current project proposes to expand on previously collected data from a human clinical trial addressing this question. In a recent study, we used simultaneous PET-fMRI imaging to triangulate dynamic changes in brain dopamine signaling, functional brain activity/connectivity, and the self-reported experience of ‘high’ in 20 healthy adults receiving methylphenidate (MP) at different speeds: slow (oral 60mg) and fast (IV 0.25mg/kg) doses in a double-blind, counterbalanced, placebocontrolled study. We identified one circuit comprising the dorsal anterior cingulate cortex and its connections with the dorsal striatum, which was activated and responded only to fast (IV) MP. Activity in this circuit also activity significantly correlated with striatal dopamine dynamics (estimated with PET) and individual differences in ‘high’ ratings. While compelling, these imaging findings are limited in scope and correlational. We aim to build on this study via two components: Aim 1: Examine the contribution of adrenaline and noradrenaline to slow and fast drug reward. We will analyze blood data collected during the human study to see if this circuit’s activity/connectivity correlates with plasma levels of adrenaline and noradrenaline. MP also increases brain concentrations of these two signaling molecules2,3 and it is important to test whether noradrenaline contributes to this circuit’s involvement in fast drug reward. Aim 2: Test causality of the circuit for fast dopamine dynamics. We will perform a series of experiments in rats. We will use chemogenetic techniques to test if inhibiting this circuit during fast MP delivery can block conditioned place preference to IV MP. This study will provide causal evidence for a circuit selective for fast drug reward.
Rosario Jaime-Lara, PhD, FNP-BC (NIAAA) and Rodolfo Flores-Garcia, PhD (NIMH)
2021 - 2022
Project Title:
Establishing a mouse of alcohol drinking during conflict
Abstract:
Impaired decision-making is often reported in Alcohol Used Disorder (AUD) and obesity-related disorders, with many patients reporting difficulty managing the intention to limit their drinking/eating despite facing negative health consequences (e.g., driving under the influence arrests and social repercussions). However, the mechanisms by which alcohol impacts decision-making during conflict remains unclear. Furthermore, highly palliative foods and alcohol have intersecting neurobiological mechanisms and behavioral effects, including shared neurological reward pathways and compulsive reward-seeking behavior, respectively. Thus, developing and establishing an animal model to study conflict resolution in the context of alcohol-drinking following dietary exposure to high-fat diets (HFD) would allow us to characterize how alcohol affects behavioral strategies for resolving approach-avoidance conflict and how HFDs interact with alcohol to impact decision-making processes. Establishing this model will be an important first step towards identifying novel mechanisms by which alcohol and a HFD affects decision-making.
Previous models to examine the effects of alcohol on approach-avoidance behavior limit rodents to a dichotomy between approaching both a reward and an aversive stimulus or avoiding a reward and an aversive stimulus. To this end, we propose assessing conflict resolution in approach-avoidance conflict in a task that allows rodents to both, seek rewards, and avoid aversive outcomes within a given trial. Thus, we have worked together to establish a platform-mediated avoidance (PMA) to assess approach avoidance conflict resolution. Our results reveal that mice can adapt their behavior to changes in reward and punishment contingencies to maximize rewards while minimizing punishments. Our data support the utility of the PMA task in assessing short-and long-term strategies in the resolution of motivational conflict in mice. Thus, this task more comprehensively captures the complexities of decision-making, beyond dichotomous choice models, allowing animals to uniquely strategize their decision making during conflict. These complexities more closely capture some elements of human decision-making. Therefore, our main goal is to use this procedure to characterize how alcohol seeking behavior in the presence of threats affects approach-avoidance strategies in mice and examine how a history of HFD feeding affects alcohol drinking behaviors during conflict.
Seed Grant Contacts
Peter Manza, Ph.D
Seed Grant Program Officer
peter.manza@nih.gov
Adam Caccavano, Ph.D
Seed Grant Program Officer
adam.caccavano@nih.gov
Valerie Darcey, Ph.D., M.S., R.D.
Seed Grant Program Director
valerie.darcey@nih.gov
Paule Joseph, CRNP, Ph.D.
Seed Grant Program Director
paule.joseph@nih.gov
Sebastian Peña-Vargas
CCB Program Analyst
sebastian.penavargas@nih.gov