Abstract
Background In children, hearing loss has been associated with hyperactivity, disturbed social interaction, and risk of cognitive disturbances. Mechanistic explanations of these relations sometimes involve language. To investigate the effect of hearing loss on behavioral deficits in the absence of language, we tested the impact of hearing loss in juvenile rats on motor, social, and cognitive behavior and on physiology of prefrontal cortex.
Methods Hearing loss was induced in juvenile (postnatal day 14) male Sprague-Dawley rats by intracochlear injection of neomycin under general anaesthesia. Sham-operated and non-operated hearing rats served as controls. One week after surgery auditory brainstem response (ABR) measurements verified hearing loss or intact hearing in sham-operated and non-operated controls. All rats were then tested for locomotor activity (open field), coordination (Rotarod), and for social interaction during development in weeks 1, 2, 4, 8, 16, and 24 after surgery. From week 8 on, rats were trained and tested for spatial learning and memory (4-arm baited 8-arm radial maze test). In a final setting, neuronal activity was recorded in the medial prefrontal cortex (mPFC).
Results In the open field deafened rats moved faster and covered more distance than sham-operated and non-operated controls from week 8 on (both p<0.05). Deafened rats showed significantly more play fighting during development (p<0.05), whereas other aspects of social interaction, such as following, were not affected. Learning of the radial maze test was not impaired in deafened rats (p>0.05), but rats used less next-arm entries than other groups indicating impaired concept learning (p<0.05). In the mPFC neuronal firing rate was reduced and enhanced irregular firing was observed. Moreover, oscillatory activity was altered, both within the mPFC and in coherence of mPFC with the somatosensory cortex (p<0.05).
Conclusions Hearing loss in juvenile rats leads to hyperactive behavior and pronounced play-fighting during development, suggesting a causal relationship between hearing loss and cognitive development. Altered neuronal activities in the mPFC after hearing loss support such effects on neuronal networks outside the central auditory system. This animal model provides evidence of developmental consequences of juvenile hearing loss on prefrontal cortex in absence of language as potential confounding factor.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- ABR
- auditory brainstem response
- AI
- asymmetry index
- ANOVA
- analysis of variance
- BS
- broad spikes
- DI
- dispersion index
- ECoGs
- electrocorticograms
- FR
- Firing rate
- ISI
- inter-spike interval
- LFP
- local field potentials
- mPFC
- medial prefrontal cortex
- NS
- narrow Spikes
- PND
- postnatal day
- RME
- reference memory errors
- SMCtx
- sensorimotor cortex
- SU
- single unit
- WME
- working memory error