Title: Beyond Motivation and Reward Seeking: Ventral Pallidum Contributions to Negative Affective States
Speaker: Doç.Dr. Güneş Ünal
Date: 7 May, Thursday 16:30
Place: Aysel Sabuncu Brain Research Center Seminar Room (SC-106)
Abstract:
The ventral pallidum (VP) is a key basal forebrain structure classically implicated in motivation and reward, often described as a node where motivation is translated into action. Utilizing several techniques in rats, we examine the broader affective functions of the VP beyond reward seeking. Combining classical and viral tract-tracing with immunohistochemistry, optogenetic and chemogenetic manipulations, behavioral assays, fiber photometry, in vivo electrophysiology, and computational modeling, we investigate how distinct VP neuronal populations contribute to behavioral activation, coping, and avoidance, particularly under aversive conditions. Selective neurotoxic lesions targeting GABAergic or cholinergic VP neurons revealed that both populations contribute to behavioral despair, a rodent model of depressive-like behavior. We then delineated projection-specific mechanisms, focusing on VP outputs to amygdaloid nuclei and the Bed Nucleus of the Stria Terminalis, identifying putative GABAergic subpopulations that preferentially target the basolateral amygdala. Through network modeling we postulate that theta-rhythmic VP input may shape local network oscillations linked to stress-related behaviors. We further examined high-level prefrontal inputs to the VP, and found that prelimbic and infralimbic projections exert dissociable effects, with infralimbic inputs primarily targeting inhibitory hDlx-expressing neurons to promote behavioral activation, suppress fear expression, and induce place preference, while prelimbic inputs convey aversive signals and drive avoidance. Inhibition of hDlx-expressing inhibitory VP neurons increased social avoidance and impaired contextual fear encoding, whereas pathway-specific optogenetic activation produced opposing effects on social behavior via projections to the lateral habenula and ventral tegmental area. Finally, we identified a distinct population of VP neurons expressing CaMKIIα whose functions do not overlap with canonical cell types, showing that these neurons regulate global behavioral arousal, as their inhibition induces social withdrawal and passivity, whereas their activation promotes movement, and that they engage opposing downstream circuits to support active coping via midbrain dopaminergic pathways and avoidance via the lateral habenula. Together, these findings establish the VP as a central regulator of affective state, integrating motivational and aversive signals to drive distinct behavioral outcomes through projection-specific mechanisms.
Bio:
Assoc. Prof. Güneş Ünal is a neuroscientist based in the Department of Psychology at Boğaziçi University. He completed his undergraduate education at the same institution between 2004 and 2008, graduating as valedictorian. He was then admitted to the Neuroscience PhD Program at Rutgers University, where his thesis focused on the electrophysiological properties of the perirhinal cortex. He completed the integrated doctoral program in 3.5 years with a GPA of 4.00/4.00 and continued at the same institute as a postdoctoral researcher for 1.5 years. In 2013, he was awarded the Blaschko European Research Fellowship and joined the Department of Pharmacology at the University of Oxford, where he also served as a Junior Research Fellow at Linacre College. In 2017, he returned to Boğaziçi University and established the Behavioral Neuroscience Laboratory. His research focuses on the neuronal mechanisms underlying fear memory, depression, and anxiety, as well as the interaction between reward and stress circuits, using rodent and avian models. The laboratory employs a multidisciplinary approach, integrating neuroanatomical, electrophysiological, pharmacological, optogenetic and chemogenetic, behavioral, and computational methods. It also examines the behavioral pharmacology of rapid-acting atypical antidepressants, the effects of sensorimotor stimuli on mood, and experimental paradigms based on animal-robot interaction. His research has been supported by EMBO, COST, TÜBİTAK, TÜSEB, and YÖK-ADEP. Dr. Ünal has received the Boğaziçi University Outstanding Achievement Awards in Teaching and Research, the Science Academy BAGEP Award, and the METU Parlar Foundation Incentive Award.