Effect Of Early Enriched Environment Exposure On The Plasticity Of Auditory Function In Central Auditory System And The Underlying Mechanism

Enriched environment (EE) has an important role in the development and plasticity of the brain, while the early experience-dependent plasticity during the critical period is a major research field for sensory system. These two highly fruitful fields, namely, sensory-cortical plasticity and EE, are combined together in a novel attempt to investigate the effects of the EE-induced plasticity. The present study used rats as animal model to find out the underlying mechanism of how early EE exposure influenced the functional plasticity of central auditory system, through behavior, electro-physiological and molecular biological methods.This dissertation includes three parts as follow:1. Enriched environment-induced auditory spatial sensitivity of the ratRats were raised in enriched environment from postnatal day 7 to day 56, the EE condition was renew in several days to keep novelty. We used 12 EE rat and 11 CON rats for the study. By testing behavioral tasks via auditory cues, we have shown that EE improved the number of correct scores, but decreased the reaction time and azimuth deviation in behavioral performance of sound-azimuth discrimination. By in vivo extracellular recording, we have shown that EE enhanced the directional sensitivity of neurons in the primary auditory cortex. For example, EE rats had a smaller spatial receptive field, sharper frequency tuning curve and directional selective curve of auditory neurons compared with normal rats. Our findings indicate that early exposure to EE increases directional sensitivity. These results provide an insight into developmental plasticity in the auditory system.2. Molecular mechanism of improved spatial sensitivity of the rat by early EE exposureBy western blotting and brain slice recording, we investigate the expression level changes of several cortical developmental related receptors and amplitude changes of the long-term potentiation between the EE, CON and PE rats. We found that early EE exposure significantly increased the expression level of NMDA receptor subunits, NR1, NR2A and NR2B; AMPA receptor subunit GluR2; GABAA receptor subunits, α1 andβ3 of the auditory cortex. In addition, the ratios between NR2A and NR2B, GABAAα1 and GABAAα3 were also increased. The expression changes tendency in the inferior colliculus was almost the same with the auditory cortex, that is, significant increases were found in NR1, NR2A, NR2B, GluR2, GABAAα1 and GABAAβ3. The results of LTP recording indicated that, the EE rats have higher fEPSP amplitude than CON and PE rats under normal induced condition. When incubated with APV (an antagonist of NMDA receptor) or DNQX (an antagonist of AMPA receptor), the increase amplitude of LTP were both partly inhibited in the two groups. However, compared with the CON and PE rats, the amplitudes were still higher in the EE rat in those cases. All these results above indicated that early EE exposure may influence the functional plasticity of the auditory system by regulating the excitatory and inhibitory circuits simultaneously.3. Maintenance of enriched environment-induced auditory functional plasticity of the ratIn this part, we used EE recovery rats (which return to normal condition for two months) as model, investigated the maintenance of early EE exposure induced changes of auditory system by behavior, electrophysiological and molecular biological methods. We found that, compared with the age-matched control, the EE rats still had better performance. As to A1 neurons, the spatial sensitivity was enhanced, expressed by a sharper frequency tuning curve, smaller spatial receptive field, and a more selective directional curve of the EE rats. In addition, we also detected significant increases in GABAAreceptor al,β3 subunits; NMDA receptor NR2A, NR2B subunits; AMPA receptor GluR2 subunit protein expression; and in the ratios of GABAAα1/GABAAα3 and NR2A/NR2B. In particular, the variation rate of all inhibitory receptor expressions was significantly higher than that of the excitatory receptor expressions in early EE exposed rats. These observations indicate the persistent higher expression levels of the GABAergic and glutamatergic receptors expression induced by early EE exposure, especially enhancement of GABAergic inhibition in the auditory cortex, might be responsible for the maintenance of improved effects in auditory spatial sensitivity.