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Juvenile rodents and other altricial mammals react with calming, immobility, and postural modifications to parental pickup, a set of behaviors referred to as the transport response. 1,2,3,4,5 Here, we investigate sensory mechanisms underlying the rat transport response. Grasping rat pups in anterior neck positions evokes strong immobility and folding up of feet, whereas more posterior grasping has lesser effects on immobility and foot position. Transport responses are enhanced by slow (1 Hz), and even more so by fast (4 Hz), gentle shaking and translation, features consistent with parental transport. With lateral grasping, the forepaw below the grasping position points downward and the forepaw lateral to the grasping position points upward and medially. Such forepaw adjustments put the pup's center of gravity below the grasping point, optimizing pup transportability. Tactile stimuli on the back, belly, tail, whisker, dorsal forepaws, and dorsal hind-paws do not significantly affect behavior of anterior-neck-held pups. Instead, ground contact, or paw stimulation consistent with ground contact, disrupts transport responses. We identify afferents mediating transport response by examining membrane labeling with FM 1-43 6 following anterior neck grasping. We observe a dense innervation of the anterior-neck-skin region (∼30 terminals/mm2). We find an age-related decrease of cytochrome oxidase reactivity in the rat somatosensory cortical neck representation, a possible correlate to developmental decrease in pup transport response. We conclude that anterior neck grasping and loss of ground contact trigger calming and postural adjustments for parental transport in rat pups, responses putatively driven from the densely innervated anterior neck skin. [Display omitted] • Anterior neck grasp, 4 Hz motion, and translation enhance the transport response • Touch simulating ground contact reverses transport immobility • Neck somatosensory cortex thins in development • Anterior-neck-skin afferents are labeled with transport response induction Ni et al. uncover mechanisms underlying rat pup transport response (TR). Anterior neck grasp, 4-Hz shake, and translation promote TR; reversal occurs with ground simulation. Anterior neck sensory endings labeled after TR; neck cortex thins in development. Mechano-sensory neck skin afferents may specialize for offspring-maternal cooperative transport. [ABSTRACT FROM AUTHOR]

Author(s): Yihui Cui [1, 2]; Yan Yang [1, 2]; Zheyi Ni [1]; Yiyan Dong [1]; Guohong Cai [3]; Alexandre Foncelle [4, 5]; Shuangshuang Ma [1]; Kangning Sang [1]; Siyang Tang [...]

The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the anti-reward center, the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants., Author(s): Yan Yang [1, 2]; Yihui Cui [1, 2]; Kangning Sang [1, 2]; Yiyan Dong [1]; Zheyi Ni [1]; Shuangshuang Ma [1]; Hailan Hu (corresponding author) [1, 2] The discovery [...]

Social competition determines hierarchical social status, which profoundly influences animals' behavior and health. The dorsomedial prefrontal cortex (dmPFC) plays a fundamental role in regulating social competitions, but it was unclear how the dmPFC orchestrates win- and lose-related behaviors through its downstream neural circuits. Here, through whole-brain c-Fos mapping, fiber photometry, and optogenetics- or chemogenetics-based manipulations, we identified anatomically segregated win- and lose-related neural pathways downstream of the dmPFC in mice. Specifically, layer 5 neurons projecting to the dorsal raphe nucleus (DRN) and periaqueductal gray (PAG) promote social competition, whereas layer 2/3 neurons projecting to the anterior basolateral amygdala (aBLA) suppress competition. These two neuronal populations show opposite changes in activity during effortful pushes in competition. In vivo and in vitro electrophysiology recordings revealed inhibition from the lose-related pathway to the win-related pathway. Such antagonistic interplay may represent a central principle in how the mPFC orchestrates complex behaviors through top-down control., Competing Interests: Declaration of interests H.H. is a member of the advisory board of Neuron., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Juvenile rodents and other altricial mammals react with calming, immobility and folding up of feet to parental pickup, a set of behaviors referred to as transport response. Here we investigate sensory mechanisms underlying the rat transport response. Grasping rat pups in anterior neck positions evokes strong immobility and folding up of feet, whereas more posterior grasping positions have lesser effects on immobility and foot position. Transport responses are enhanced by slow (1Hz) and even more so by fast (4Hz) gentle shaking and translation of the pup, features consistent with parental transport. In response to lateral grasping, the forepaw below the grasping position points downwards and the forepaw lateral to the grasping position points upwards and medially. Such forepaw adjustments put the pup's center of gravity below the grasping point, optimizing pup transportability along with folding up of feet and tail lifting. Tactile stimuli on the back, belly, tail, whisker, dorsal forepaws and dorsal hind-paws do not significantly affect the behaviour of anterior-neck-held pups. Instead, ground contact or paw stimulation consistent with ground contact disrupts transport responses. We identify afferents mediating the transport response by examining membrane labelling with FM1-43 following anterior neck grasping. We observe a dense innervation of the anterior neck skin region (~30 terminals/ mm 2 ). We also observed an age-related decrease of cytochrome oxidase reactivity in the rat somatosensory cortical neck representation, a possible correlate to the developmental decrease in the pup transport response. We conclude anterior neck grasping and loss of ground contact trigger calming and postural adjustments for parental transport in rat pups, responses putatively driven from the densely innervated anterior neck skin.

Ketamine has been found to have rapid and potent antidepressant activity. However, despite the ubiquitous brain expression of its molecular target, the N -methyl-d-aspartate receptor (NMDAR), it was not clear whether there is a selective, primary site for ketamine's antidepressant action. We found that ketamine injection in depressive-like mice specifically blocks NMDARs in lateral habenular (LHb) neurons, but not in hippocampal pyramidal neurons. This regional specificity depended on the use-dependent nature of ketamine as a channel blocker, local neural activity, and the extrasynaptic reservoir pool size of NMDARs. Activating hippocampal or inactivating LHb neurons swapped their ketamine sensitivity. Conditional knockout of NMDARs in the LHb occluded ketamine's antidepressant effects and blocked the systemic ketamine-induced elevation of serotonin and brain-derived neurotrophic factor in the hippocampus. This distinction of the primary versus secondary brain target(s) of ketamine should help with the design of more precise and efficient antidepressant treatments.