Vocal development in dystonic rats

Abstract

Vocal production, which requires the generation and integration of laryngeal and respiratory motor patterns, can be impaired in dystonia, a disorder believed due to dysfunction of sensorimotor pathways in the central nervous system. Herein, we analyze vocal and respiratory abnormalities in the dystonic (dt) rat, a well-characterized model of generalized dystonia. The dt rat is a recessive mutant with haploinsufficiency of Atcay which encodes the neuronally restricted protein caytaxin. Olivocerebellar functional abnormalities are central to the dt rat's truncal and appendicular dystonia and could also contribute to vocal and respiratory abnormalities in this model system. Differences in vocal repertoire composition were found between homozygote and wild-type dt rat pups developing after 3 weeks of life. Those spectro-temporal differences were not paralleled by differences in vocal activity or maximum lung pressures during quiet breathing and vocalization. However, breathing rhythm was slower in homozygote pups. This slower breathing rhythm persisted into adulthood. Given that cerebellectomy eliminates truncal and appendicular dystonia in the dt rat, we hypothesize that the altered breathing patterns stem either from a disturbance in the maturation of respiratory pattern generators or from deficient extracerebellar caytaxin expression affecting normal respiratory pattern generation. The altered breathing rhythm associated with vocal changes in the murine model resembles aspects of vocal dysfunction that are seen in humans with sporadic dystonia.

Rapid development of mature vocal patterns of ultrasonic calls in a fast-growing rodent, the yellow steppe lemming (Eolagurus luteus)

“…Another different ontogenetic pathway (towards the longer and lower-frequency USV calls) is characteristic of laboratory rats [1,12,47,48,50,51,53,55,56,58,[96][97][98]. Rat pup 40-kHz USV calls decrease in frequency during the first 2-3 wk of life [12,47,50] followed by increase in frequency at about 4 wk [12,48,53], and splitting after 4 wk to mature vocal patterns of 22-kHz and 50-kHz USV calls [1,51,58,96,97], which both display a further decrease of fundamental frequency to senescence [55,56,98]. At the same time, duration of rat USV calls remains stable until 3 wk, then suddenly decreases [12] and increases again from 6 wk up to senescence [55,56,98].…”

“…Ultrasonic vocalizations (USV) of laboratory rodents represent age-dependent indicators of animal emotional arousal [1][2][3][4][5][6] and may serve for modeling human diseases and the evaluation of drugs and medicaments effects [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The overwhelmingly preferred mice USV model [1,8,10,[21][22][23][24] is applicable for USV ontogeny [7,16,19,20,[25][26][27][28][29][30][31][32][33].…”

“…golden hamsters Mesocricetus auratus, vocal traits are relatively resistant to the destabilizing effects across generations [46]. These facts explain a growing research interest to non-traditional wild-type animal models of vocal ontogeny [1,12,39,[46][47][48][49][50][51][52][53].…”

“…The ontogenetic changes of USV calls may differ between species [12,39,49,[54][55][56]. The age-related growth affects USV acoustic variables [12,26,29,39,49,[55][56][57], percentage of different contour shapes (flat, chevron, wave, upward, downward) [7,39,49,54,[58][59][60][61][62][63][64][65] and percentage of different nonlinear phenomena: frequency jumps, biphonations and subharmonics [39,49].…”

“…Key acoustic variables, fundamental frequency (f0) and duration, reflecting developmental changes of USV calls, display different ontogenetic trajectories across species. For example, in ontogeny of laboratory rat, duration overall increases while the f0 decreases [12,55,56]. In ontogeny of laboratory mouse, both duration and f0 decrease [26,29].…”