Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.

Neural circuits underlying auditory fear conditioning have been extensively studied. Here we identified a previously unexplored pathway from the lateral amygdala (LA) to the auditory cortex (ACx), and found that selective silencing of this pathway using chemo-and optogenetic approaches impairs fear memory retrieval. Dual-color in vivo two-photon imaging of mouse ACx showed pathwayspecific increases in the formation of LA axon boutons, dendritic spines of ACx layer-5 pyramidal cells, and putative LA-ACx synaptic pairs after auditory fear conditioning. Furthermore, co-imaging of pre-and postsynaptic structures showed that essentially all new synaptic contacts were made by adding new partners to existing synaptic elements. Together, these findings identify an amygdalocortical projection that plays an important role in fear memory expression and is selectively modified by associative fear learning, and unravel a distinct architectural rule for synapse formation in the adult brain. 2 IntroductionAssociative learning enables an animal to adapt to and survive in a complex environment. In classical auditory fear conditioning, animals learn to associate a neutral stimulus (a sound) with a foot-shock, and exhibit fear responses to the sound presentation. Amygdala is critical for the formation of auditory fear memory 1 .Previous studies have also shown that the auditory cortex (ACx) is required for auditory fear learning [2][3][4] , and that fear conditioning could induce rapid and long-term changes in neuronal responses and spine dynamics in ACx. However, which synapses in ACx underwent modification remain unclear.Long-term in vivo two-photon imaging has been used to monitor structural remodeling of synaptic connectivity, as was shown by changes in presynaptic boutons or postsynaptic spines that represent the formation or elimination of synapses.Previous studies have shown that sensory experience and learning can induce changes in the turnover of presynaptic axon boutons 9 and postsynaptic dendritic spines. To further explore synaptic dynamics in specific pathways, concurrent imaging of preand post-synaptic structures in identified connections is required. This approach, although successfully applied in studying synaptic dynamics in hippocampal slices 16 , has not been used for in vivo imaging of the neocortex.In this study, combining tracing methods with electron microscopy (EM), we identified a projection to ACx that originates from lateral amygdala (LA), the major 3 input region of the amygdala. Chemo-and optogenetic silencing of LA axons in ACx during fear recall test greatly reduced animals' fear responses, suggesting that the LAACx pathway plays an important role in the expression of fear memory. By coimaging labeled axons originating from brain regions projecting to ACx and apical dendrites of pyramidal neurons in ACx, we were able to monitor the dynamics of putative synaptic pairs in specific pathways in vivo. We observed a selective increase in bouton and spine formation at LA-ACx connections after fear con...

Highlights d The ipsi-and contralateral spinoparabrachial pathways are functionally distinct d The ipsilateral spinoparabrachial pathway mediates nocifensive behavior d Tacr1 + neurons in the PBN represent the major target of spinal projection d The PBN relays nociceptive information to the ILN via glutamatergic synapses

Highlights d Novel ovine SNPs of the male-specific region of Y chromosome were developed d Y chromosome of domestic sheep contains four different paternal lineages d Lineages C and B predominate in breeds of primitive traits and fat tail, respectively d Expansions of sheep correlate with various phenotypic traits and breeding goals

Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

The orbitofrontal cortex (OFC) encodes expected outcomes and plays a critical role in flexible, outcome-guided behavior. The OFC projects to primary visual cortex (V1), yet the function of this top-down projection is unclear. We find that optogenetic activation of OFC projection to V1 reduces the amplitude of V1 visual responses via the recruitment of local somatostatin-expressing (SST) interneurons. Using mice performing a Go/No-Go visual task, we show that the OFC projection to V1 mediates the outcome-expectancy modulation of V1 responses to the reward-irrelevant No-Go stimulus. Furthermore, V1-projecting OFC neurons reduce firing during expectation of reward. In addition, chronic optogenetic inactivation of OFC projection to V1 impairs, whereas chronic activation of SST interneurons in V1 improves the learning of Go/No-Go visual task, without affecting the immediate performance. Thus, OFC top-down projection to V1 is crucial to drive visual associative learning by modulating the response gain of V1 neurons to non-relevant stimulus.

, 4 , 5 -T r i s u b s t i t u t e d -, 2 , 3 -t r i a z o l e v i a O n e -P o t R e a c t i o n P r o m o t e d b y C o p p e r ( I ) S a l tAbstracts: A method for the regiospecific synthesis of 1,4,5-trisubstituted-1,2,3-triazole catalyzed by copper(I) iodide was developed. This is the first example of a regiospecific synthesis of 5-iodo-1,4-disubstituted-1,2,3-triazole, which can be further elaborated to a range of 1,4,5-trisubstituted-1,2,3-triazole derivatives.