Neuron
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The lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents in diverse nocifensive responses have remained largely uncharacterized. ⋯ Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drives escape behaviors, whereas activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin-expressing neurons, which span cytoarchitecturally distinct domains of the lPBN, are required for aversive learning.
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During neonatal development, sensory cortices generate spontaneous activity patterns shaped by both sensory experience and intrinsic influences. How these patterns contribute to the assembly of neuronal circuits is not clearly understood. Using longitudinal in vivo calcium imaging in un-anesthetized mouse pups, we show that spatially segregated functional assemblies composed of interneurons and pyramidal cells are prominent in the somatosensory cortex by postnatal day (P) 7. ⋯ This aberrant pattern effectively blocks interneuron apoptosis, causing increased survival of parvalbumin and somatostatin interneurons. Furthermore, the effect of GABA on apoptosis is mediated by inputs from medial ganglionic eminence (MGE)-derived but not caudal ganglionic eminence (CGE)-derived interneurons. These findings indicate that immature MGE interneurons are fundamental for shaping GABA-driven activity patterns that balance the number of interneurons integrating into maturing cortical networks.
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Despite enormous progress in machine learning, artificial neural networks still lag behind brains in their ability to generalize to new situations. Given identical training data, differences in generalization are caused by many defining features of a learning algorithm, such as network architecture and learning rule. ⋯ Brains, on the other hand, generalize across comparatively drastic changes in the sensory input all the time. We highlight some shortcomings of state-of-the-art learning algorithms compared to biological brains and discuss several ideas about how neuroscience can guide the quest for better inductive biases by providing useful constraints on representations and network architecture.
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Pain is a subjective sensory experience that can, mostly, be reported but cannot be directly measured or quantified. Nevertheless, a suite of biomarkers related to mechanisms, neural activity, and susceptibility offer the possibility-especially when used in combination-to produce objective pain-related indicators with the specificity and sensitivity required for diagnosis and for evaluation of risk of developing pain and of analgesic efficacy. Such composite biomarkers will also provide improved understanding of pain pathophysiology.
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Uncontrollable itch-scratching cycles lead to serious skin damage in patients with chronic itch. However, the neural mechanism promoting the itch-scratching cycle remains elusive. Here, we report that tachykinin 1 (Tac1)-expressing glutamatergic neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) facilitate the itch-scratching cycle. ⋯ Importantly, activation of Tac1-expressing neurons induced robust spontaneous scratching and grooming behaviors. The scratching behavior evoked by Tac1-expressing neuron activation was suppressed by ablation of spinal neurons expressing gastrin-releasing peptide receptor (GRPR), the key relay neurons for itch. These results suggest that Tac1-expressing neurons in the l/vlPAG promote itch-scratching cycles.