Dataset Information

The ventral midline thalamus coordinates prefrontal-hippocampal neural synchrony during vicarious trial and error.

ABSTRACT: When faced with difficult choices, the possible outcomes are considered through a process known as deliberation. In rats, deliberation is thought to be reflected by pause-and-reorienting behaviors, better known as vicarious trial and errors (VTEs). While VTEs are thought to require medial prefrontal cortex (mPFC) and dorsal hippocampal (dHPC) interactions, no empirical evidence has yet demonstrated such a dual requirement. The nucleus reuniens (Re) of the ventral midline thalamus is anatomically connected with both the mPFC and dHPC, is required for HPC-dependent spatial memory tasks, and is critical for mPFC-dHPC neural synchronization. Currently, it is unclear if, or how, the Re is involved in deliberation. Therefore, by examining the role of the Re on VTE behaviors, we can better understand the anatomical and physiological mechanisms supporting deliberation. Here, we examined the impact of Re suppression on VTE behaviors and mPFC-dHPC theta synchrony during asymptotic performance of a HPC-dependent delayed alternation (DA) task. Pharmacological suppression of the Re increased VTE behaviors that occurred with repetitive choice errors. These errors were best characterized as perseverative behaviors, in which some rats repeatedly selected a goal arm that previously yielded no reward. We then examined the impact of Re suppression on mPFC-dHPC theta synchrony during VTEs. We found that during VTEs, Re inactivation was associated with a reduction in mPFC-dHPC theta coherence and mPFC-to-dHPC theta directionality. Our findings suggest that the Re contributes to deliberation by coordinating mPFC-dHPC neural interactions.

SUBMITTER: Stout JJ

PROVIDER: S-EPMC9243057 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The midline thalamus bidirectionally connects the medial prefrontal cortex (mPFC) and hippocampus (HC) creating a unique cortico-thalamo-cortical circuit fundamental to memory and executive function. While the anatomical connectivity of midline thalamus has been thoroughly investigated, little is known about its cellular organization within each nucleus. Here we used immunohistological techniques to examine cellular distributions in the midline thalamus based on the calcium binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). We also examined these calcium binding proteins in a population of reuniens cells known to project to both mPFC and HC using a dual fluorescence retrograde adenoassociated virus-based tracing approach. These dual reuniens mPFC-HC projecting cells, in particular, are thought to be important for synchronizing mPFC and HC activity. First, we confirmed the absence of PV+ neurons in the midline thalamus. Second, we found a common pattern of CR+ and CB+ cells throughout midline thalamus with CR+ cells running along the nearby third ventricle (3V) and penetrating the midline. CB+ cells were consistently more lateral and toward the middle of the dorsal-ventral extent of the midline thalamus. Notably, single-labeled CR+ and CB+ zones were partially overlapping and included dual-labeled CR+ /CB+ cells. Within RE, we also observed a CR and CB subzone specific diversity. Interestingly, dual mPFC-HC projecting neurons in RE expressed none of the calcium binding proteins examined, but were contained in nests of CR+ and CB+ cells. Overall, the midline thalamus was well organized into CR+ and CB+ rich zones distributed throughout the region, with dual mPFC-HC projecting cells in reuniens representing a unique cell population. These results provide a cytoarchitectural organization in the midline thalamus based on calcium binding protein expression, and set the stage for future cell-type specific interrogations of the functional role of these different cell populations in mPFC-HC interactions.

Project description:Abnormalities in functional connectivity between brain areas have been postulated as an important pathophysiological mechanism underlying schizophrenia. In particular, macroscopic measurements of brain activity in patients suggest that functional connectivity between the frontal and temporal lobes may be altered. However, it remains unclear whether such dysconnectivity relates to the aetiology of the illness, and how it is manifested in the activity of neural circuits. Because schizophrenia has a strong genetic component, animal models of genetic risk factors are likely to aid our understanding of the pathogenesis and pathophysiology of the disease. Here we study Df(16)A(+/-) mice, which model a microdeletion on human chromosome 22 (22q11.2) that constitutes one of the largest known genetic risk factors for schizophrenia. To examine functional connectivity in these mice, we measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wild-type mice, hippocampal-prefrontal synchrony increased during working memory performance, consistent with previous reports in rats. Df(16)A(+/-) mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal-prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A(+/-) mice to learn the task and increased more slowly during task acquisition. These data suggest how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level. Our findings further suggest that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia.

Dataset Information

The ventral midline thalamus coordinates prefrontal-hippocampal neural synchrony during vicarious trial and error.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets