Encoding of danger by parabrachial CGRP neurons

Abstract

Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide (CGRP) in the parabrachial nucleus (PBN) relay sensory signals that contribute to satiation and pain-induced fear behavior, but it is unknown how they encode these distinct processes. By recording calcium transients in vivo from individual CGRPPBN neurons, we reveal that most neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). These same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel food or by an auditory cue that was previously paired with electrical foot shocks. Correspondingly, silencing CGRPPBN neurons attenuates expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioral states that limit harm in response to potential threats.

Septal GABAergic Inputs to CA1 Govern Contextual Memory Retrieval

“…By encoding the intensity of multisensory cues 15 , septo-hippocampal GABAergic boutons may calibrate behavioral or autonomic responses 12 upon contextual re-exposure. Further, the enhanced response of MS CA1 cells to conditioned stimuli following learning parallels observations in the parabrachial nucleus 22 , and suggests a mechanism underlying the efficiency of memory recall. The ability of the MS GABA -CA1 pathway to prevent the induction of PV+ cell activation during retrieval is also analogous to the disinhibition of excitatory outputs in prefrontal cortex that gates fear expression 23 .…”

Neural circuit mechanism underlying the feeding controlled by insula-central amygdala pathway

“…Neurons in the CeA receive inputs from diverse brain regions, some of which have been demonstrated to regulate behaviors related to feeding (Campos et al, 2016;Palmiter, 2018;Schiff et al, 2018;Wang et al, 2018). For example, it was reported that neurons in the lateral parabrachial nucleus (LPB) that express calcitonin gene-related protein (CGRP) relay danger information and project to the CeA to suppress food intake (Campos et al, 2018;Carter et al, 2013); neurons in insular cortex that encode bitter taste project to CeA to convey negative valence (Schiff et al, 2018;Wang et al, 2018). More recently, Gehrlach et al expressed ChR2 in insular cortex under CamK2a promoter and demonstrated that activation of the insulaàCeA pathway suppresses feeding, increases anxiety and induces other aversive behaviors (Gehrlach et al, 2019).Interestingly, when we used AAVretro-Cre in CeA and Cre-dependent ChR2 in insular cortex, we only observed feeding suppression but not anxiety or other aversive behaviors.…”

Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice

“…Information related to injury reaches the brain largely through NK1R-positive projection neurons of the superficial dorsal horn that terminate massively in the parabrachial area of the brainstem and to a lesser extent within the thalamus (35,51). The parabrachial area is crucial for supplying information to forebrain areas that generate the affective-motivational component of pain (52,53) whereas thalamic afferents terminate within cortical areas concerned with both pain discrimination and affect (51). Forebrain activation can in turn regulate dorsal horn sensitivity by activating descending controls from the brainstem to the spinal cord (3,12,54).…”