Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia.

The unique fast spiking (FS) phenotype of cortical parvalbumin-positive (PV) neurons depends on the expression of multiple subtypes of voltage-gated potassium channels (Kv). PV neurons selectively express Kcns3, the gene encoding Kv9.3 subunits, suggesting that Kcns3 expression is critical for the FS phenotype. KCNS3 expression is lower in PV neurons in the neocortex of subjects with schizophrenia, but the effects of this alteration are unclear, because Kv9.3 subunit function is poorly understood. Therefore, to assess the role of Kv9.3 subunits in PV neuron function, we combined gene expression analyses, computational modeling, and electrophysiology in acute slices from the cortex of Kcns3-deficient mice. Kcns3 mRNA levels were ~ 50% lower in cortical PV neurons from Kcns3-deficient relative to wildtype mice. While silent per se, Kv9.3 subunits are believed to amplify the Kv2.1 current in Kv2.1-Kv9.3 channel complexes. Hence, to assess the consequences of reducing Kv9.3 levels, we simulated the effects of decreasing the Kv2.1-mediated current in a computational model. The FS cell model with reduced Kv2.1 produced spike trains with irregular inter-spike intervals, or stuttering, and greater Na+ channel inactivation. As in the computational model, PV basket cells (PVBCs) from Kcns3-deficient mice displayed spike trains with strong stuttering, which depressed PVBC firing. Moreover, Kcns3 deficiency impaired the recruitment of PVBC firing at gamma frequency by stimuli mimicking synaptic input observed during cortical UP states. Our data indicate that Kv9.3 subunits are critical for PVBC physiology and suggest that KCNS3 deficiency in schizophrenia could impair PV neuron firing, possibly contributing to deficits in cortical gamma oscillations in the illness.

Conductas de riesgo auditivo y acción del mecanismo de protección coclear en adolescentes / Auditory risk behaviors and the action of cochlear protection mechanism in adolescent

La exposición a ruido no ocupacional y a la música a alto nivel sonoro, constituye un creciente factor de riesgo de pérdida auditiva en adolescentes. Estudios internacionales postulan que una función importante del Sistema Eferente Medial (SEM) es proteger el oído interno frente al ruido mediante un mecanismo reflejo y que puede ser evaluado a través de la Supresión Contralateral (SC) de las otoemisiones acústicas transitorias (TEOAEs). El mecanismo subyacente de este fenómeno no se conoce en su totalidad y los antecedentes sobre el tema son escasos. En esta investigación se analizó la relación entre la Exposición General a Música (EGM), el estado de la función auditiva y el mecanismo de protección coclear. Participaron 91 adolescentes con edades entre 14 y 15 años. Se evaluaron dos dimensiones (a) Psicosocial: se examinó la EGM con un cuestionario de actividades extraescolares y (b) auditiva o sea el funcionamiento del SEM mediante SC de las TEOAEs y los perfiles audiométricos con audiometrías. Los resultados mostraron que la SC no influyó estadísticamente en los perfiles audiométricos y categorías de exposición. Sin embargo, los resultados de la SC se orientan hacia la menor magnitud de efecto supresor, disminución en la respuesta total en relación al descenso de los umbrales auditivos y en relación con las categorías alta y baja de EGM. Es necesario promover trabajos destinados al comportamiento de riesgo auditivo conjuntamente con el mecanismo protector del SEM. De esta manera se podrá contribuir en la identificación temprana de la sensibilidad auditiva en adolescentes expuestos a ruido no ocupacional.

Non-occupational exposure to noise, such as loud music sound level is an increasing risk factor for hearing loss in adolescents. International studies propose that an important function of the medial efferent system (MES) is protect the inner ear against noise by a reflex mechanism and can be evaluated through Contralateral Suppression (CS) of transient otoacoustic emissions (TEOAEs) to analyzing the presence or absence of suppressive effect. The absence of suppressive effect is considered a possible alteration of the MES and the role it exerts on the regulation of the outer hair cells. The underlying mechanism of this phenomenon is not known totality and the background about this topic are limited. However, researches suggests that MES would have an important role in protection against acoustic overstimulation under the hypothesis that a hearing with the presence of suppressive effect would tend to be more protected against exposure to high noise levels while ears with no effect suppressor may be more vulnerable to noise exposure. In this research the relationship between the General Exposure to Music (MGE), the state of hearing function and cochlear protection mechanism were analyzed in 91 adolescents with 14/15 years old, with male predominance, of two technical schools of the city of Córdoba (Argentina). Were evaluated the following dimensions: (a) Psychosocial: MGE through an Out of School Activities Questionnaire to know in detail the participation in five recreational activities to finally analyze the MGE and (b) Audiological: assessment of audiometric profiles, as a subjective method, by audiometry in the conventional frequency ranges (250-8000) Hz and an extended high frequency audiometry (8000-16000) Hz; function of MES assessment, objective method, through CS of TEOAEs to determine the presence or absence of suppressive effect. The study CS of TEOAEs consisted of two steps: Step 1, application of TEOAEs of an ear in form ipsilateral without acoustic stimulation in the contralateral ear (CAS) and Step 2, application of TEOAEs in the ear ipsilateral while applying CAS. Was considered presence of suppressive effect when there was a reduction in the response after the CAS that is to say when the difference of values obtained in the total response with and without CAS was positive. At the same time, was considered absence of suppressive effect in cases of maintained or increased the response after the CAS, obtaining a value of zero or negative. The results of the research showed that in the group with presence of suppressive effect the most of ears is among moderate and high categories of MGE with a lower average magnitude of suppressive effect and a decreased amplitude of the total response in the high category of MGE than the media category. Regarding audiometry the ears with presence of suppressive effect showed higher magnitude in the group of normal hearing thresholds compared with the group of descended hearing thresholds. The results related to CS of the TEOAEs statistically did not influence in the audiometric profiles and the exposure categories. However the results of the CS were oriented towards the smaller magnitude of suppressive effect, decreased total response related with the descended hearing thresholds and high and low categories of MGE. It is necessary to promote and intensify researches in relation to the auditory risk behaviors together with the protection mechanism of MES. In this way, more researches can contribute to the early identification of hearing sensitivity in adolescents exposed to non-occupational noise. It is important to implement a Psycho-Auditory Screening to collaborate in the prevention and promotion of hearing health.

Hearing and loud music exposure in 14-15 years old adolescents.

Adolescent exposure to loud music has become a social and health problem whose study demands a holistic approach. The aims of the current study are: (1) To detect early noise-induced hearing loss among adolescents and establish its relationship with their participation in musical recreational activities and (2) to determine sound immission levels in nightclubs and personal music players (PMPs). The participants consisted in 172 14-15 years old adolescents from a technical high school. Conventional and extended high frequency audiometry, transient evoked otoacoustic emissions and questionnaire on recreational habits were administered. Hearing threshold levels (HTLs) were classified as: normal (Group 1), slightly shifted (Group 2), and significantly shifted (Group 3). The musical general exposure (MGE), from participation in recreational musical activities, was categorized in low, moderate, and high exposure. The results revealed an increase of HTL in Group 2 compared with Group 1 (P < 0.01), in Group 3 compared with Group 2 (P < 0.05) only in extended high frequency range, in Group 3 compared with Group 1 (P < 0.01). Besides, a decrease in mean global amplitude, reproducibility and in frequencies amplitude in Group 2 compared with Group 1 (P < 0.05) and in Group 3 compared with Group 1 (P < 0.05). A significant difference (P < 0.05) was found in Group 1's HTL between low and high exposure, showing higher HTL in high exposure. The sound immission measured in nightclubs (107.8-112.2) dBA and PMPs (82.9-104.6) dBA revealed sound levels risky for hearing health according to exposure times. It demonstrates the need to implement preventive and hearing health promoting actions in adolescents.

Hearing and loud music exposure in a group of adolescents at the ages of 14-15 and retested at 17-18.

Young people expose themselves to potentially damaging loud sounds while leisure activities and noise induced hearing loss is diagnosed in increasing number of adolescents. Hearing and music exposure in a group of adolescents of a technical high school was assessed at the ages of: 14-15 (test) and 17-18 (retest). The aims of the current study were: (1) To compare the auditory function between test and retest; (2) to compare the musical exposure levels during recreational activities in test and retest; (3) to compare the auditory function with the musical exposure along time in a subgroup of adolescents. The participants in the test were 172 male; in the retest, this number was reduced to 59. At the test and retest the conventional and extended high frequency audiometry, transient evoked otoacoustic emissions (TEOAEs) and recreational habits questionnaire were performed. In the test, hearing threshold levels (HTLs) were classified as: Normal (Group 1), slightly shifted (Group 2), and significantly shifted (Group 3); the Musical General Exposure (MGE), categorized in: Low, moderate, high, and very high exposure. The results revealed a significant difference (P < 0.0001) between test and retest in the HTL and global amplitude of TEOAEs in Group 1, showing an increase of the HTL and a decrease TEOAEs amplitude. A subgroup of adolescents, with normal hearing and low exposure to music in the test, showed an increase of the HTL according with the categories of MGE in the retest. To implement educational programs for assessing hearing function, ear vulnerability and to promote hearing health, would be advisable.