Agha, H. | Search bioRxiv

bioRxiv2026

Astrocytes mediate the pro-cognitive value of α7nAChRs and of α7nAChR-targeting therapeutics

The 7-nicotinic acetylcholine receptor (7nAChR) has driven extensive research over the past three decades for its pro-cognitive potential. It is the leading druggable target for the cognitive deficits associated with schizophrenia and has motivated major pharmaceutical and clinical efforts to ameliorate similar impairments in other neurological disorders, such as Alzheimers disease (AD). Yet, a systematic evaluation of the role played by 7nAChR in cognition, and its mechanistic underpinnings, is still lacking. Here we report that 7nAChRs on principal and inhibitory forebrain neurons are largely inconsequential to mouse behavior, including in domains that are most sensitive to schizophrenia-related cognitive impairments. By contrast, loss of 7nAChR from astrocytes produces profound behavioral alterations that are cognitive domain-specific, are time-of-day dependent, coincide with reduced levels of the N-methyl D-aspartate receptor (NMDAR) co-agonist D-serine, and are fully restored by D-serine supplementation. Further, an 7nAChR partial agonist previously evaluated in Phase III trials for cognitive enhancement in schizophrenia and AD fails to augment behavior in mice lacking astrocytic 7nAChRs. Together, these findings identify astrocytes and D-serine/NMDAR signaling as a central mechanism through which 7nAChR, a major drug target, promotes cognitive behavior.

neuroscience↗

bioRxiv2025

Potato dihaploids uncover diverse alleles to facilitate diploid potato breeding

Commercial potato in North America is a clonal autotetraploid crop, which complicates breeding. Efforts are underway to convert potato to a diploid inbred-hybrid crop that is amenable to additional breeding strategies and allows breeders to more quickly respond to demands for crop improvement. With the goal of preserving haplotypes developed over the last 200 years of selection, diploid potato breeding in the US started with the creation of diploids from tetraploid commercial varieties and advanced breeding lines through prickle pollination. This is an effective but slow method which presents a barrier to entry for individual breeding programs. Therefore, we developed 97 publicly available dihaploids (diploids from prickle pollination of tetraploids) as a resource for diploid breeding in the U.S. These clones contain the majority of alleles in the US breeding population for three market classes: chips, russets, and fresh market reds. To facilitate genomic informed breeding, all clones have been resequenced using short read sequencing technology, and we have developed de novo assemblies based on PacBio HiFi long reads for 20 individuals. As an illustration of how these data will be used in breeding, we explored the maturity locus (StCDF1) and identified 15 different alleles. The majority of dihaploids were heterozygous for early and late alleles, resulting in intermediate maturity. Beyond informing breeding, this data facilitates investigations into potato genomics. The dihaploid population is both highly heterozygous and incredibly diverse on a population level. In particular, there is extensive structural diversity, including copy number variation, segregating within the population. This contrasts with a relatively low genome-wide historical recombination rate ({rho}). Taken together, these findings indicate that potato is highly diverse, with much of that diversity found within long linkage blocks.

plant biology↗