Sensory organ damage induces a host of cellular and physiological changes in the periphery and the brain. Here, we show that some aspects of auditory processing recover after profound cochlear denervation due to a progressive, compensatory plasticity at higher stages of the central auditory pathway. Lesioning >95% of cochlear nerve afferent synapses, while sparing hair cells, in adult mice virtually eliminated the auditory brainstem response and acoustic startle reflex, yet tone detection behavior was nearly normal. As sound-evoked responses from the auditory nerve grew progressively weaker following denervation, sound-evoked activity in the cortex – and to a lesser extent the midbrain – rebounded or surpassed control levels. Increased central gain supported the recovery of rudimentary sound features encoded by firing rate, but not features encoded by precise spike timing such as modulated noise or speech. These findings underscore the importance of central plasticity in the perceptual sequelae of cochlear hearing impairment.

Ouabain application to the round window can selectively destroy type-I spiral ganglion cells, producing an animal model of auditory neuropathy. To assess the long-term effects of this deafferentation on synaptic organization in the organ of Corti and cochlear nucleus, and to ask whether surviving cochlear neurons show any post-injury plasticity in the adult, we quantified the peripheral and central synapses of type-I neurons at posttreatment times ranging from 1 to 3 months. Measures of normal DPOAEs and greatly reduced auditory brainstem responses (ABRs) confirmed the neuropathy phenotype. Counts of presynaptic ribbons and postsynaptic glutamate receptor patches in the inner hair cell area decreased with post-exposure time, as did counts of cochlear nerve terminals in the cochlear nucleus. Although these counts provided no evidence of new synapse formation via branching from surviving neurons, the regular appearance of ectopic neurons in the inner hair cell area suggested that neurite extension is not uncommon. Correlations between pathophysiology and histopathology showed that ABR thresholds are very insensitive to even massive neural degeneration, whereas the amplitude of ABR wave 1 is a better metric of synaptic degeneration.

Due to limited spectral resolution, cochlear implants (CIs) do not convey pitch information very well. Pitch cues are important for perception of music and tonal language; it is possible that music training may improve performance in both listening tasks. In this study, we investigated music training outcomes in terms of perception of music, lexical tones, and sentences in 22 young (4.8 to 9.3 years old), prelingually deaf Mandarin-speaking CI users. Music perception was measured using a melodic contour identification (MCI) task. Speech perception was measured for lexical tones and sentences presented in quiet. Subjects received 8 weeks of MCI training using pitch ranges not used for testing. Music and speech perception were measured at 2, 4, and 8 weeks after training was begun; follow-up measures were made 4 weeks after training was stopped. Mean baseline performance was 33.2%, 76.9%, and 45.8% correct for MCI, lexical tone recognition, and sentence recognition, respectively. After 8 weeks of MCI training, mean performance significantly improved by 22.9, 14.4, and 14.5 percentage points for MCI, lexical tone recognition, and sentence recognition, respectively (p < .05 in all cases). Four weeks after training was stopped, there was no significant change in posttraining music and speech performance. The results suggest that music training can significantly improve pediatric Mandarin-speaking CI users’ music and speech perception.

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<b><i>Introduction:</i></b> In older US nursing home (NH) residents, there is limited research on the prevalence of physical frailty, its potential dynamic changes, and its association with cognitive impairment in older adults’ first 6 months of NH stay. <b><i>Methods:</i></b> Minimum Data Set (MDS) 3.0 is the national database on residents in US Medicare-/Medicaid-certified NHs. MDS 3.0 was used to identify older adults aged ≥65 years, newly admitted to NHs during January 1, 2014, and June 30, 2016, with life expectancy ≥6 months at admission and NH length of stay ≥6 months (<i>N</i> = 571,139). MDS 3.0 assessments at admission, 3 months, and 6 months were used. In each assessment, physical frailty was measured by FRAIL-NH (robust, prefrail, and frail) and cognitive impairment by Brief Interview for Mental Status and Cognitive Performance Scale (none/mild, moderate, and severe). Demographic characteristics and diagnosed conditions were measured at admission, while presence of pain and receipt of psychotropic medications were at each assessment. Distribution of physical frailty and its change over time by cognitive impairment were described. A nonproportional odds model was fitted with a generalized estimation equation to longitudinally examine the association between physical frailty and cognitive impairment, adjusting for demographic and clinical characteristics. <b><i>Results:</i></b> Around 60% of older residents were physically frail in the first 6 months. Improvement and worsening across physical frailty levels were observed. Particularly, in those who were prefrail at admission, 23% improved to robust by 3 months. At admission, 3 months, and 6 months, over 37% of older residents had severe cognitive impairment and about 70% of those with cognitive impairment were physically frail. At admission, older residents with moderate cognitive impairment were 35% more likely (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.33–1.37) and those with severe impairment were 74% more likely (aOR: 1.74, 95% CI: 1.72–1.77) to be frail than prefrail/robust, compared to those with none/mild impairment. The association between the 2 conditions remained positive and consistently increased over time. <b><i>Discussion/Conclusion:</i></b> Physical frailty was prevalent in NHs with potential to improve and was strongly associated with cognitive impairment. Physical frailty could be a modifiable target, and interventions may include efforts to address cognitive impairment.

Wild tomatoes (Solanum peruvianum) are important genomic resources for tomato research and breeding. Development of a foreign DNA-free CRISPR-Cas delivery system has potential to mitigate public concern about genetically modified organisms. Here, we established a DNA-free CRISPR-Cas9 genome editing system based on an optimized protoplast regeneration protocol of S. peruvianum, an important resource for tomato introgression breeding. We generated mutants for genes involved in small interfering RNAs (siRNA) biogenesis, RNA-DEPENDENT RNA POLYMERASE 6 (SpRDR6) and SUPPRESSOR OF GENE SILENCING 3 (SpSGS3); pathogen-related peptide precursors, PATHOGENESIS-RELATED PROTEIN-1 (SpPR-1) and PROSYSTEMIN (SpProSys); and fungal resistance (MILDEW RESISTANT LOCUS O, SpMlo1) using diploid or tetraploid protoplasts derived from in vitro-grown shoots. The ploidy level of these regenerants was not affected by PEG-Ca2+-mediated transfection, CRISPR reagents, or the target genes. By karyotyping and whole genome sequencing analysis, we confirmed that CRISPR-Cas9 editing did not introduce chromosomal changes or unintended genome editing sites. All mutated genes in both diploid and tetraploid regenerants were heritable in the next generation. spsgs3 null T0 regenerants and sprdr6 null T1 progeny had wiry, sterile phenotypes in both diploid and tetraploid lines. The sterility of the spsgs3 null mutant was partially rescued, and fruits were obtained by grafting to wild-type stock and pollination with wild-type pollen. The resulting seeds contained the mutated alleles. Tomato yellow leaf curl virus proliferated at higher levels in spsgs3 and sprdr6 mutants than in the wild type. Therefore, this protoplast regeneration technique should greatly facilitate tomato polyploidization and enable the use of CRISPR-Cas for S. peruvianum domestication and tomato breeding.

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