Whole‐brain monosynaptic inputs to lateral periaqueductal gray glutamatergic neurons in mice

Abstract

ObjectiveThe lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive behaviors. Currently, the whole‐brain monosynaptic inputs to LPAG glutamatergic neurons are unknown. This study aims to explore the structural framework of the underlying neural mechanisms of LPAG glutamatergic neurons.MethodsThis study used retrograde tracing systems based on the rabies virus, Cre‐LoxP technology, and immunofluorescence analysis.ResultsWe found that 59 nuclei projected monosynaptic inputs to the LPAG glutamatergic neurons. In addition, seven hypothalamic nuclei, namely the lateral hypothalamic area (LH), lateral preoptic area (LPO), substantia innominata (SI), medial preoptic area, ventral pallidum, posterior hypothalamic area, and lateral globus pallidus, projected most densely to the LPAG glutamatergic neurons. Notably, we discovered through further immunofluorescence analysis that the inputs to the LPAG glutamatergic neurons were colocalized with several markers related to important neurological functions associated with physiological behaviors.ConclusionThe LPAG glutamatergic neurons received dense projections from the hypothalamus, especially nuclei such as LH, LPO, and SI. The input neurons were colocalized with several markers of physiological behaviors, which show the pivotal role of glutamatergic neurons in the physiological behaviors regulation by LPAG.

The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors

“…Because of its extensive connections with the cortex and various brainstem nuclei, PAG serves as a critical midbrain hub for sensory-motor integration (see Figure 1 for details; Zare et al, 2019 ; Schottelkotte and Crone, 2022 ; Ma et al, 2023 ). It primarily receives input from regions such as the medial prefrontal cortex (mPFC), central amygdala (CeA), anterior cingulate cortices (ACC), bed nucleus of the stria terminalis (BST), hypothalamus, and dorsal premammillary nucleus (PMD), allowing for the relay and integration of sensory information from diverse modalities ( Benarroch, 2012 ; Faull et al, 2019 ; Zare et al, 2019 ; Schottelkotte and Crone, 2022 ).…”

Effects of cognitive training and behavior modification on aggressive behavior and sleep quality in schizophrenia

“…In the United States, individuals with this condition face an average potential loss of 28.5 years of life (3)(4)(5)(6). Pharmacological and brain imaging studies have demonstrated that disruptions in dopamine neurotransmission can result in psychiatric symptoms, such as delusions and hallucinations, whereas aberrant glutamate signaling may contribute to negative and cognitive symptoms (7)(8)(9). Nonetheless, there is an indication that various brain regions and circuits are extensively implicated, leading to a range of effects.…”