GluR2, a major subunit in AMPA receptor, plays an important role in brain functional activity. We studied the effect of music exposure during development on the expression level of GluR2 proteins in the auditory cortex (AC) and anterior cingulate cortex (ACC) of SD rats. Rats were divided into three groups, Music1 (exposed to Nostalgy) group, Music2 (exposed to Wishmaster) group, and control (no music exposure) group. For music exposure groups, rats were exposed to music from postnatal day (PND) 14, and the expression levels of GluR2 proteins were determined at PND 28, 42 and 56. For the control group, the expression levels of GluR2 proteins were determined at PND1, 3, 5, 7, 9, 11, 14, 21, 28, 42, and 56. Results showed an age-dependent expression of GluR2 proteins in control rats. In AC, exposure to Music2 dramatically increased the expression of GluR2, while exposure to Music1 had no effect. In ACC, we found remarkable discrepancies in time-dependent expression of GluR2 between music exposed rats and control rats. These results indicate that exposure to music can modify the expression level of GluR2 protein in AC and ACC.

Nakamoto, Kyle T., Jiping Zhang, and Leonard M. Kitzes. Temporal nonlinearity during recovery from sequential inhibition by neurons in the cat primary auditory cortex. J Neurophysiol 95: 1897–1907, 2006. First published December 7, 2005; doi:10.1152/jn.00625.2005. Auditory stimuli occur most often in sequences rather than in isolation. It is therefore necessary to understand how responses to sounds occurring in sequences differ from responses to isolated sounds. Cells in primary auditory cortex (AI) respond to a large set of binaural stimuli when presented in isolation. The set of responses to such stimuli presented at one frequency comprises a level response area. A preceding binaural stimulus can reduce the size and magnitude of level response areas of AI cells. The present study focuses on the effects of the time interval between a preceding stimulus and the stimuli of a level response area in pentobarbital-anesthetized cats. After the offset of a preceding stimulus, the ability of AI cells to respond to succeeding stimuli varies dynamically in time. At short interstimulus intervals (ISI), a preceding stimulus can completely inhibit responses to succeeding stimuli. With increasing ISIs, AI cells respond first to binaural stimuli that evoke the largest responses in the control condition, i.e., not preceded by a stimulus. Recovery rate is nonlinear across the level response area; responses to these most-effective stimuli recover to 70% of control on average 187 ms before responses to other stimuli recover to 70% of their control sizes. During the tens to hundreds of milliseconds that a level response area is reduced in size and magnitude, the selectivity of AI cells is increased for stimuli that evoke the largest responses. This increased selectivity results from a temporal nonlinearity in the recovery of the level response area which protects responses to the most effective binaural stimuli. Thus in a sequence of effective stimuli, a given cell will respond selectively to only those stimuli that evoke a strong response when presented alone.

In the auditory cortex, the properties of NMDA receptors depend primarily on the ratio of NR2A and NR2B subunits. NR2B subunit expression is high at the beginning of critical period and lower in adulthood. Because NMDA receptors are crucial in triggering long-term potentiation (LTP) and long-term depression, developmental or experience-dependent modification of NMDAR subunit composition is likely to influence synaptic plasticity. To examine how NMDA subunit change during postnatal development affect the adult synaptic plasticity, we employed chronic ifenprodil blockade of NR2B subunits and analyzed evoked field potentials in adult C57BL/6 mice auditory cortex (AC). We found that chronic loss of NR2B activity led to a decline in LTP magnitude in the AC of adult mice. Adding NMDA to the artificial cerebrospinal fluid (ACSF) in blocked mice had the opposite effect, producing LTP magnitudes at or exceeding those found in treated or untreated animals. These results suggest that, even in adulthood when NR2B expression is downregulated, these receptor subunits play an important role in experience-dependent plasticity of mouse auditory cortex. Blockade from P60 did not result in any decrease of LTP amplitude, suggesting that chronic block in postnatal period may permanently affect cortical circuits so that they cannot produce significant LTP in adulthood.

NMDA receptors have been well shown to be involved in neuronal plasticity. In order to understand the role of NR2B subtypeNMDA receptors in auditory function development, the present study investigated the effect of early auditory deprivation on the expression of NR2B mRNA in rat auditory cortex (AC) during postnatal development. For normal rats, the NR2B mRNA expression was highest at birth (postnatal day 1 [P1]) and declined rapidly to low level during adulthood. However, during the critical period of rat auditory development (two to three weeks after birth), there was a transient NR2B expression peak on postnatal day 21 (P21). For the auditory-deprived rats, the general declining trend of NR2B mRNA expression from birth to adult was similar to that observed in the normal group, whereas the expression level from P15 to P27 was significantly lower than normal and the transient peak on P21 disappeared. In both groups, the distribution pattern of NR2B mRNA-positive neurons was also examined in various layers and dorsal, medial and ventral subdistricts of AC. There is no significant effect on the spatial expression of the NR2B mRNA in the AC between normal and deprived group. Our results indicated that the early auditory deprivation decreased the expression levels of NR2B mRNA in AC during the critical period of rat auditory development, suggesting that NR2B plays an important role in the developmental plasticity of auditory function in rats.

Zhang, Jiping, Kyle T. Nakamoto, and Leonard M. Kitzes. Modulation of level response areas and stimulus selectivity of neurons in cat primary auditory cortex. J Neurophysiol 94: 2263–2274, 2005. First published May 25, 2005; 10.1152/jn.01207.2004. Sounds commonly occur in sequences, such as in speech. It is therefore important to understand how the occurrence of one sound affects the response to a subsequent sound. We approached this question by determining how a conditioning stimulus alters the response areas of single neurons in the primary auditory cortex (AI) of barbiturate-anesthetized cats. The response areas consisted of responses to stimuli that varied in level at the two ears and delivered at the characteristic frequency of each cell. A binaural conditioning stimulus was then presented ≥50ms before each of the stimuli comprising the level response area. An effective preceding stimulus alters the shape and severely reduces the size and response magnitude of the level response area. This ability of the preceding stimulus depends on its proximity in the level domain to the level response area, not on its absolute level or on the size of the response it evokes. Preceding stimuli evoke a nonlinear inhibition across the level response area that results in an increased selectivity of a cortical neuron for its preferred binaural stimuli. The selectivity of AI neurons during the processing of a stream of acoustic stimuli is likely to be restricted to a portion of their level response areas apparent in the tone-alone condition. Thus rather than being static, level response areas are fluid; they can vary greatly in extent, shape and response magnitude. The dynamic modulation of the level response area and level selectivity of AI neurons might be related to several tasks confronting the central auditory system.

Zhang, Jiping, Kyle T. Nakamoto, and Leonard M. Kitzes. Binaural interaction revisited in the cat primary auditory cortex. J Neurophysiol 91: 101–117, 2004. First published September 24, 2003; 10.1152/jn.00166.2003. The binaural interactions of neurons were studied in the primary auditory cortex (AI) of barbiturate-anesthetized cats with a matrix of binaural tonal stimuli varying in both interaural level differences (ILD) and average binaural level (ABL). The purpose of this study was to determine: 1) the distribution of preferred binaural combinations (PBCs) of a large population of neurons and its relationships with binaural interactions and binaural monotonicity; 2) whether monaural responses are predictive of binaural responses; and 3) whether there is a restricted set of representative binaural stimulus configurations that could effectively classify the binaural nteractions. Binaural interactions were often diverse in the matrix and dependent on both ABL and ILD. Compared with previous studies, a higher proportion of mixed binaural interaction type and a lower proportion of EO/I type were found. No monaural neurons were found. Binaural responses often differed from monaural responses in the number of spikes and/or the form of the response functions. The PBCs of the majority of EO and PB neurons were in the contralateral field and midline, respectively. However, the PBCs of EE units were evenly distributed across the contralateral and ipsilateral fields. The majority of the nonmonotonic neurons responded most strongly to lower ABLs, whereas the majority of monotonic neurons responded most strongly to higher ABLs. This study demonstrated that in AI a restricted set of binaural stimulus configurations is not sufficient to reveal the binaural responses properties. Also, monaural responses are not predictive of binaural responses.

Nakamoto, Kyle T., Jiping Zhang, and Leonard M. Kitzes. Response patterns along an isofrequency contour in cat primary auditory cortex (AI) to stimuli varying in average and interaural levels. J Neurophysiol 91: 118–135, 2004. First published October 1, 2003; 10.1152/jn.00171.2003. The topographical response of a portion of an isofrequency contour in primary cat auditory cortex (AI) to a series of monaural and binaural stimuli was studied. Responses of single neurons to monaural and a matrix of binaural characteristic frequency tones, varying in average binaural level (ABL) and interaural level differences (ILD), were recorded. The topography of responses to monaural and binaural stimuli was appreciably different. Patches of cells that responded monotonically to increments in ABL alternated with patches that responded nonmonotonically to ABL. The patches were between 0.4 and 1 mm in length along an isofrequency contour. Differences were found among monotonic patches and among nonmonotonic patches. Topographically, activated and silent populations of neurons varied with both changes in ILD and changes in ABL, suggesting that the area of responsive units may underlie the coding of sound level and sound location.

This article reviews our recent studies of brief and short-term corticofugal modulation of signal processing in the central nucleus of the inferior colliculus (ICc) by electrical stimulation in the primary auditory cortex (AC). When cortical electrical stimulation was synchronized with an acoustic stimulus, auditory responses of ICc neurons were either inhibited or facilitated and the modulative effect typically vanished within 5-10 s after the stimulation. When cortical electrical stimulation synchronized with an acoustic stimulus was repetitively delivered for 30 min, corticofugal modulation of collicular responses typically persisted up to 40 min after the stimulation. In the frequency domain, cortical electrical stimulation decreased the excitatory frequency tuning curves (FTCs) and asymmetrically increased the lateral inhibitory FTCs of corticofugally inhibited ICc neurons but produced the opposite effect on corticofugally facilitated ICc neurons. Cortical electrical stimulation facilitated auditory responses of neurons in the external nucleus of the inferior colliculus (ICx) while electrical stimulation in the ICx decreased auditory responses of ICc neurons. Auditory responses of simultaneously recorded ICx and ICc neurons varied in opposite ways during cortical electrical stimulation or drug application to recorded ICx neurons. In the amplitude domain, cortical electrical stimulation compressed rate-amplitude functions so as to increase the slope of rate^amplitude functions of ICc neurons. This modulative effect decreased with increasing stimulus amplitude. The possible biological relevance of these findings is discussed.

This study examined the role of GABAergic inhibition on direction-dependent sharpening of frequency tuning curves (FTCs) in bat inferior collicular (IC) neurons under free field stimulation conditions. The minimum threshold (MT) at the neurons best frequency (BF) and the sharpness (Q, Q, Q) of FTCs of most IC neurons increased as the sound direction changed from contralateral azimuths to 10 20 30 ipsilateral azimuths. The application of GABA antagonist, bicuculline, lowered all MTs but the application did not abolish A direction-dependent variation in MT. MTs determined during bicuculline application at 40 ipsilateral were still significantly higher than those determined at 408 contralateral (two-tailed paired t-test, P, 0.0001). In contrast, although application of bicuculline essentially had no effect on the BFs of IC neurons, it differentially broadened neurons FTCs at different azimuths abolishing the direction-dependent sharpening of frequency tuning (i.e. Q values, two-tailed paired t-test, P, 0.01). These data indicate that GABAergic inhibition makes n an important contribution to the direction-dependent frequency tuning of most IC neurons. Ó 2000 Elsevier Science B.V. All rights reserved.

Corticofugal regulation of excitatory and inhibitory frequency tuning curves FTCs.of neurons in the central nucleus of bat inferior colliculus ICc. was studied by electrical stimulation of the primary auditory cortex AC stimulation. under free field stimulation conditions using a two-tone inhibition paradigm. AC stimulation narrowed the excitatory FTCs and asymmetrically expanded the lateral inhibitory FTCs of corticofugally inhibited ICc neurons. The opposite results were observed for excitatory and inhibitory FTCs of corticofugally facilitated ICc neurons. These data support previous reports that corticofugal systems work together with widespread lateral inhibition to regulate subcortical frequency processing.