The mechanisms by which hearing selectivity is elaborated and refined in early development are very incompletely determined. In this study, we documented contributions of progressively maturing inhibitory influences on the refinement of spectral and temporal response properties in the primary auditory cortex. Inhibitory receptive fields (IRFs) of infant rat auditory cortical neurons were spectrally far broader and had extended over far longer duration than did those of adults. The selective refinement of IRFs was delayed relative to that of excitatory receptive fields by an Ϸ2-week period that corresponded to the critical period for plasticity. Local application of a GABA A receptor antagonist revealed that intracortical inhibition contributes to this progressive receptive field maturation for response selectivity in frequency. Conversely, it had no effect on the duration of IRFs or successive-signal cortical response recovery times. The importance of exposure to patterned acoustic inputs was suggested when both spectral and temporal IRF maturation were disrupted in rat pups reared in continuous, moderate-intensity noise. They were subsequently renormalized when animals were returned to standard housing conditions as adults.

The basis for multiple representations of equivalent frequency ranges in auditory cortex was studied with physiological and anatomical methods. Our goal was to trace the convergence of thalamic, commissural, and corticocortical information upon two tonotopic fields in the cat, the primary auditory cortex (AI) and the anterior auditory field (AAF). Both fields are among the first cortical levels of processing. After neurophysiological mapping of characteristic frequency, we injected different retrograde tracers at separate, frequency-matched loci in AI and AAF. We found differences in their projections that support the notion of largely segregated parallel processing streams in the auditory thalamus and cerebral cortex. In each field, ipsilateral cortical input amounts to approximately 70% of the number of cells projecting to an isofrequency domain, while commissural and thalamic sources are each approximately 15%. Labeled thalamic and cortical neurons were concentrated in tonotopically predicted regions and in smaller loci far from their spectrally predicted positions. The few double-labeled thalamic neurons (<2%) are consistent with the hypothesis that information to AI and AAF travels along independent processing streams despite widespread regional overlap of thalamic input sources. Double labeling is also sparse in both the corticocortical and commissural systems ( approximately 1%), confirming their independence. The segregation of frequency-specific channels within thalamic and cortical systems is consistent with a model of parallel processing in auditory cortex. The global convergence of cells outside the targeted frequency domain in AI and AAF could contribute to context-dependent processing and to intracortical plasticity and reorganization.

. Two tonotopic areas, the primary auditory cortex (AI) and the anterior auditory field (AAF), are the primary cortical fields in the cat auditory system. They receive largely independent, concurrent thalamocortical projections from the different thalamic divisions despite their hierarchical equivalency. The parallel streams of thalamic inputs to AAF and AI suggest that AAF neurons may differ from AI neurons in physiological properties. Although a modular functional organization in cat AI has been well documented, little is known about the internal organization of AAF beyond tonotopy. We studied how basic receptive field parameters (RFPs) are spatially organized in AAF with single-and multiunit recording techniques. A distorted tonotopicity with an underrepresentation in midfrequencies (1 and 5 kHz) and an overrepresentation in the high-frequency range was found. Spectral bandwidth (Q-values) and response threshold were significantly correlated with characteristic frequency (CF). To understand whether AAF has a modular organization of RFPs, CF dependencies were eliminated by a nonparametric, local regression model, and the residuals (difference between the model and observed values) were evaluated. In a given isofrequency domain, clusters of low or high residual RFP values were interleaved for threshold, spectral bandwidth, and latency, suggesting a modular organization. However, RFP modules in AAF were not expressed as robustly as in AI. A comparison of RFPs between AAF and AI shows that AAF neurons were more broadly tuned and had shorter latencies than AI neurons. These physiological field differences are consistent with anatomical evidence of largely independent, concurrent thalamocortical projections in AI and AAF, which strongly suggest fieldspecific processing.

No abstract

Crickets provide a useful model to study neural processing of sound frequency. Sound frequency is one parameter that crickets use to discriminate between conspecific signals and sounds made by predators, yet little is known about how frequency is represented at the level of auditory receptors. In this paper, we study the physiological properties of auditory receptor fibers (ARFs) by making single-unit recordings in the cricket Teleogryllus oceanicus. Characteristic frequencies (CFs) of ARFs are distributed discontinuously throughout the range of frequencies that we investigated (2-40 kHz) and appear to be clustered around three frequency ranges (/=18 kHz). A striking characteristic of cricket ARFs is the occurrence of additional sensitivity peaks at frequencies other than CFs. These additional sensitivity peaks allow crickets to detect sound over a wide frequency range, although the CFs of ARFs cover only the frequency bands mentioned above. To the best of our knowledge, this is the first example of the extension of an animal's hearing range through multiple sensitivity peaks of auditory receptors.

Primary sensory cortical areas are characterized by orderly and largely independent representations of several receptive field properties. This is expressed in multiple, spatially overlaying parameter distributions, such as orientation preference, spatial frequency, and ocular dominance maps in the primary visual cortex. In the auditory cortex, two main and presumably independent representational parameters are the center frequency and the frequency extent of spectral tuning curves. Here we demonstrate interactions between cortical tonotopic gradient and spectral bandwidth modules in cat primary auditory cortex (AI). First, the spatial representation of spectral integration is not equally expressed across the whole frequency range in AI. Narrow-bandwidth modules are found only in the mid-frequency region (5-20 kHz). Thus spectral integration properties delineate three frequency regions (<5, 5-20, and >20 kHz) in cat AI. Second, the extent of spectral integration covaries with the local tonotopic gradient in the low- and mid-frequency ranges. Regions with a shallow frequency gradient tend to have narrower spectral integration than those with a steep gradient. These relationships between spectral selectivity and frequency gradient constrain forebrain models of thalamo- and corticocortical convergence and connectivity and may reflect the processing of behaviorally relevant stimulus constellations.

CACNA1I, a schizophrenia risk gene, encodes a subtype of voltage-gated T-type calcium channel Ca V 3.3. We previously reported that a patient-derived missense de novo mutation (R1346H) of CACNA1I impaired Ca V 3.3 channel function. Here, we generated Ca V 3.3-RH knock-in animals, along with mice lacking Ca V 3.3, to investigate the biological impact of R1346H (RH) variation. We found that RH mutation altered cellular excitability in the thalamic reticular nucleus (TRN), where Ca V 3.3 is abundantly expressed. Moreover, RH mutation produced marked deficits in sleep spindle occurrence and morphology throughout non-rapid eye movement (NREM) sleep, while Ca V 3.3 haploinsufficiency gave rise to largely normal spindles. Therefore, mice harboring the RH mutation provide a patient derived genetic model not only to dissect the spindle biology but also to evaluate the effects of pharmacological reagents in normalizing sleep spindle deficits. Importantly, our analyses highlighted the significance of characterizing individual spindles and strengthen the inferences we can make across species over sleep spindles. In conclusion, this study established a translational link between a genetic allele and spindle deficits during NREM observed in schizophrenia patients, representing a key step toward testing the hypothesis that normalizing spindles may be beneficial for schizophrenia patients.

The physiological characteristics of auditory receptor fibers (ARFs) of crickets, a model system for studying auditory behaviors and their neural mechanisms, are investigated. Unlike auditory receptor neurons of many animals, cricket ARFs fall into three distinct populations based on characteristic frequency (CF) [Imaizumi and Pollack, J. Neurosci. 19, 1508-1516 (1999)]. Two of these have CFs similar to the frequency component of communication signals or of ultrasound produced by predators, and a third population has intermediate CF. Here, sound-amplitude coding by ARFs is examined to gain insights to how behaviorally relevant sounds are encoded by populations of receptor neurons. ARFs involved in acoustic communication comprise two distinct anatomical types, which also differ in physiological parameters (threshold, response slope, dynamic range, minimum latency, and sharpness of tuning). Thus, based on CF and anatomy, ARFs comprise four populations. Physiological parameters are diverse, but within each population they are systematically related to threshold. The details of these relationships differ among the four populations. These findings open the possibility that different ARF populations differ in functional organization.