Social isolation uncovers a brain-wide circuit underlying context-dependent territory-covering micturition behavior

Abstract

The controlled and volitional release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the decision to release urine is modulated by external and internal factors such as environmental stimuli and social history and is transmitted to the spinal cord via the pontine micturition center (PMC). The neural pathways by which social experience and sensory stimuli interact to control PMC activity and regulate micturition are unclear. Here we establish a behavioral paradigm in which mice, depending on their strain, social experience, and immediate sensory context, display either high or low territory-covering micturition (TCM). We demonstrate that social context is represented by coordinated global activity changes in the urination network upstream of the PMC, whereas sensory context is represented by the activation of discrete nodes in the network. Furthermore, we show that the lateral hypothalamic area (LHA), which is directly upstream of PMC, is a key node that can switch micturition behavior between high and low TCM modes. SF 366.5 384.349234 798 196.872209 0.21687968 0.80839929 AAA 910.25 185.465855 587.75 179.046316 0.00360848 0.05846712 ARH 89.75 12.3119183 97 53.4290807 0.77934917 1

3D Whole-Brain Imaging Approaches to Study Brain Tumors

“…In the last decade, LSFM combined with optical tissue clearing has significantly impacted various fields such as neuroscience and developmental biology [ 64 , 77 , 82 , 83 , 84 , 85 ]. Tissue clearing methods were used to map the neuronal connections and neural activity in the mouse brain [ 72 , 73 , 86 , 87 ], generate whole-brain atlases with single-cell resolution [ 88 , 89 ], and complexly map, label, and regionally annotate the vascular topology of the normal mouse brain and in models of congenital deafness and ischemic stroke [ 90 , 91 ].…”

Choosing to urinate. Circuits and mechanisms underlying voluntary urination

“…Human imaging data has revealed a relationship between the activity in the cingulate cortex, frontal lobes, and the sensation of bladder filling [26]. In mice, the frontal lobe (including Prefrontal Cortex, PFC) is also implicated in bladder control by lesion studies [58,59] and the PFC is known to send direct glutamatergic projections to Bar Crh [60] (Figure 2d). Given the overarching role that the PFC plays in the control of motor and social behavior, it may integrate social, environment, and physiology related information.…”

“…The Lateral Hypothalamic Area (LHA) also modulates Bar, through both excitatory and inhibitory monosynaptic connections (Figure2d) [36,60]. Non-selective chemogenetic inhibition of both excitatory and inhibitory cells in the LHA promote urine marking, while chemogenetic activation prevents scent marking [60].…”

“…The Lateral Hypothalamic Area (LHA) also modulates Bar, through both excitatory and inhibitory monosynaptic connections (Figure2d) [36,60]. Non-selective chemogenetic inhibition of both excitatory and inhibitory cells in the LHA promote urine marking, while chemogenetic activation prevents scent marking [60]. When optogenetics was used to selectively activate the excitatory LHA terminals in the Bar in freely moving mice, urination was stimulated, although inconsistently, more often with a full bladder, and with an approximately half-minute temporal delay.…”