@article {67765, title = {Genetically identified amygdala-striatal circuits for valence-specific behaviors.}, journal = {Nature Neuroscience}, volume = {24}, year = {2021}, month = {2021 Oct 18}, pages = {1586-1600}, abstract = {

The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.

}, issn = {1546-1726}, doi = {10.1038/s41593-021-00927-0}, author = {Zhang, Xian and Guan, Wuqiang and Yang, Tao and Furlan, Alessandro and Xiao, Xiong and Yu, Kai and An, Xu and Galbavy, William and Ramakrishnan, Charu and Deisseroth, Karl and Ritola, Kimberly and Hantman, Adam and He, Miao and Josh Huang, Z and Li, Bo} } @article {65739, title = {A genetically defined compartmentalized striatal direct pathway for negative reinforcement.}, journal = {Cell}, volume = {181}, year = {2020}, month = {2020 Oct 1}, pages = {211}, abstract = {

The striosome compartment within the dorsal striatum has been implicated in reinforcement learning and regulation of motivation, but how striosomal neurons contribute to these functions remains elusive. Here, we show that a genetically identified striosomal population, which expresses the Teashirt family zinc finger 1 (Tshz1) and belongs to the direct pathway, drives negative reinforcement and is essential for aversive learning in mice. Contrasting a "conventional" striosomal direct pathway, the Tshz1 neurons cause aversion, movement suppression, and negative reinforcement once activated, and they receive a distinct set of synaptic inputs. These neurons are predominantly excited by punishment rather than reward and represent the anticipation of punishment or the motivation for avoidance. Furthermore, inhibiting these neurons impairs punishment-based learning without affecting reward learning or movement. These results establish a major role of striosomal neurons in behaviors reinforced by punishment and moreover uncover functions of the direct pathway unaccounted for in classic models.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2020.08.032}, author = {Xiao, Xiong and Deng, Hanfei and Furlan, Alessandro and Yang, Tao and Zhang, Xian and Hwang, Ga-Ram and Tucciarone, Jason and Wu, Priscilla and He, Miao and Palaniswamy, Ramesh and Ramakrishnan, Charu and Ritola, Kimberly and Hantman, Adam and Deisseroth, Karl and Osten, Pavel and Huang, Z Josh and Li, Bo} } @article {48267, title = {A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and Enkephalins.}, journal = {Neuron}, volume = {93}, year = {2017}, month = {2017 Jan 31}, pages = {822-39}, abstract = {

Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in\ vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds. Unexpectedly, we found that RVM GABAergic neurons facilitate mechanical pain by inhibiting dorsal horn enkephalinergic/GABAergic interneurons. We further demonstrate that these interneurons gate sensory inputs and control pain through temporally coordinated enkephalin- and GABA-mediated presynaptic inhibition of somatosensory neurons. Our results uncover a descending disynaptic inhibitory circuit that facilitates mechanical pain, is engaged during stress, and could be targeted to establish higher pain thresholds.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2017.01.008}, author = {Fran{\c c}ois, Amaury and Low, Sarah A and Sypek, Elizabeth I and Christensen, Amelia J and Sotoudeh, Chaudy and Beier, Kevin T and Ramakrishnan, Charu and Ritola, Kimberly D and Sharif-Naeini, Reza and Deisseroth, Karl and Delp, Scott L and Malenka, Robert C and Luo, Liqun and Hantman, Adam W and Scherrer, Gr{\'e}gory} }