Temporary Hearing Deprivation In Early Life Impairs Spatial Memory Of Rats

BACKGROUND:In the first year of life,more than 62%of children will experience middle ear infection,temporary hearing deprivation is common in early childhood due to the prevalence of middle ear infection.The hearing loss has been shown to alter the development of central auditory functions,but its impact on high brain functions remains largely unknown.Children with a history of middle ear infection demonstrate behavioral and attentional deficits in the classroom setting,as well as poorer academic performance.However,the impact of otitis media on children's development appears to depend on the inter-relationship between several factors,such as gender,birth status,genetic predisposition and socioeconomic status.Thus,it is unclear whether temporary hearing deprivation caused by middle ear infection have any effects on learning and memory.Sensory degradation/deprivation due to hearing loss can result in neural degradation and reduced cognitive function.The hippocampus is an essential brain structure for episodic memory and spatial memory.Learning and memory are mediated by neuronal plasticity,which includes long-term potentiation(LTP),synapto genes is modulation of intrinsic excitability,and adult neurogenesis.Thus,we put forward a temporary hearing deprivation(THD)model to study the impact on spital memory of hppocampus,and investigated the mechanism involved.METHODS:For the THD group,the tympanic membranes were perforated bilaterally at 14 postnatal days to develop early age temporary hearing deprivation.The auditory brainstem response were recorded to test the hearing loss of THD group compared to the control group.Behavioral test of Morris water maze and Y maze test were done to demonstrate the early age temporary hearing deprivation on learning and memory.Experiments involved field potential recording about imput/output function,paired pulse response and long-term potentiation,whole cell patch clamp recording about cell membrane characteristics,N-methyl-D-aspartic acid receptor(NMDA)receptor mediated miniature excitatory postsynaptic current,NMDA receptor and ?-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor(AMPA)receptor mediated evoked excitatory postsynaptic current,western blotting about NR2A and NR2B,immunohistochemistry of 5-Bromo-2'-deoxyuridine(BrdU),Golgi-Cox staining to test dendritic spine,transmission electron microscope to test postsynaptic density,retrograde tracer injections and so on.The experiments here were used to study the possible mechanisms of learning and memory impairment.RESULTS:(1)Tympanic membranes perforated bilaterally at 14 postnatal days developed early age temporary hearing deprivation by auditory brainstem response.(2)Early age temporary hearing deprivation impaired learning and memory as poorer behavioral performance in Morris water maze(MWM)and Y-maze tests.(3)Early age temporary hearing deprivation impaired learning and memory as LTP and I/O function are decreased in vivo field potential recordings.(4)The amplitude of NMDA receptor mediated miniature excitatory postsynaptic current decreased in the THD group in patch clamp recordings.(5)In patch clamp recordings,the cell membrane characteristics were not changed in the THD group,as the resting membrane potential and input resistance had no significant difference between the THD group and the control group.(6)In the western blot,the expression of NR2B was decreased,and NR2A was increased,while the ratio of NR2A/NR2B were increased in the THD group.(7)The dendritic spine of CA1 neuron were decreased in the THD group.(8)The postsynaptic density of CA1 neuron were decreased in the THD group.(9)The neurogenesis of BrdU positive neurons were less in the THD group than the control group.(10)There exists direct projection from auditory cortex to hippocampus.DISCUSSION:In this study,we demonstrate that early age temporary hearing deprivation caused by bilateral tympanic membranes perforation impairs learning and memory.Impaired ability of learning and memory in THD group was mediated by neuronal plasticity.The plasticity changed here might result from three factors in the study:(1)synaptic functional plasticity,which was shown by long-term potentiation(LTP);(2)the synaptogenesis,which was expressed by the number of dendritic spine and postsynaptic density;(3)adult neurogenesis,which was shown by BrdU+newborn neurons.In the present study,rats(P14)were underwent surgery to destroy the tympanic membranes bilaterally,without impairment of vestibular dysfunction.The surgery was straightforward to do.In the study,retrograde tracer injected in the hippocampus,which demonstrated that hippocampus received directed projection from auditory cortex.These results were in line with the report that auditory information comes to the hippocampus following two paths which are called lemniscal path and non-lemniscal path,which lead the happening that early age temporary hearing deprivation impaired adult hippocampal function.In the present study,we demonstrated for the first time that early age temporary hearing deprivation caused learning and memory damage,which is manifested in the synaptic plasticity by LTP impairment.Whole cell patch clamp recordings showed a significant decrease of NMDA receptor-mediated evoked excitatory postsynaptic currents(eEPSCs)at Sch-CA1 synapses and the NMDA/AMPA ratio in THD group.As researchers demonstrated that LTP amplitude varies in direct proportion to the NMDA/AMPA ratio.Increased NR2A/NR2B ratio constrained long-term memory.Future work may include the efforts to further understand how increased NR2A/NR2B ratio acts as a major factor affecting the pathway of synaptic plasticity and memory function caused by early age temporary hearing deprivation.As the initial abrupt decline in adult neurogenesis was paralleled by a significant reduction in MWM performance,neurogenesis was decreased in THD group in our study.It suggested that worse performance in behavior tests may have something to do with less neurogenesis.