Elsevier

Neuroscience

Volume 475, 1 November 2021, Pages 10-51
Neuroscience

Research Article
Sound Intensity-dependent Multiple Tonotopic Organizations and Complex Sub-threshold Alterations of Auditory Response Across Sound Frequencies in the Thalamic Reticular Nucleus

https://doi.org/10.1016/j.neuroscience.2021.08.027Get rights and content

Highlights

  • Auditory thalamic reticular nucleus is comprised of multiple tonotopic organizations.

  • Tonotopic gradient and clarity differ depending on sound intensity and response type.

  • Somatosensory thalami nuclei receive auditory influence of specific sound frequency.

  • Subthreshold masker sound primarily attenuates cell activities evoked by probe sound.

  • Magnitudes of masker sound effects are associated with tonotopic organizations.

Abstract

The thalamic reticular nucleus (TRN), a cluster of GABAergic cells, modulates sensory attention and perception through its inhibitory projections to thalamic nuclei. Cortical and thalamic topographic projections to the auditory TRN are thought to compose tonotopic organizations for modulation of thalamic auditory processing. The present study determined tonotopies in the TRN and examined interactions between probe and masker sounds to obtain insights into temporal processing associated with tonotopies. Experiments were performed on anesthetized rats, using juxta-cellular recording and labeling techniques. Following determination of tonotopies, effects of sub-threshold masker sound stimuli on onset and late responses evoked by a probe sound were examined. The main findings are as follows. Tonotopic organizations were recognized in cell location and axonal projection. Tonotopic gradients and their clarities were diverse, depending on sound intensity, response type and the tiers of the TRN. Robust alterations in response magnitude, latency and/or burst spiking took place following masker sounds in either a broad or narrow range of frequencies that were close or far away from the probe sound frequency. The majority of alterations were suppression recognizable up to 600 ms in the interval between masker and probe sounds, and directions of alteration differed depending on the interval. Finally, masker sound effects were associated with tonotopic organizations. These findings suggest that the auditory TRN is comprised of sound intensity-dependent multiple tonotopic organizations, which could configure temporal interactions of auditory information across sound frequencies and impose complex but spatiotemporally structured influences on thalamic auditory processing.

Introduction

The thalamic reticular nucleus (TRN), a cluster of GABAergic cells receiving excitatory inputs from cortical areas and thalamic nuclei, modulates thalamic sensory processing through its inhibitory projections to thalamic nuclei (Pinault, 2004). At such a position strategically important for the regulation of interactive neural processing between the cortex and thalamus, the TRN is considered to play a pivotal role in modulation of sensory attention and perception (Weese et al., 1999, McAlonan et al., 2008, Wimmer et al., 2015, Wolff et al., 2021). The TRN is comprised of several sensory sectors (Pinault, 2004), and each of the sensory sectors is thought to be primarily engaged in modulation of thalamic processing of its relevant sensory modality based on distinctive anatomical connectivity associated with a modality-specific functional organization such as tonotopy, retinotopy or somatotopy (Shosaku et al., 1984, Pinault et al., 1995, Fitzgibbon et al., 1999, Fitzgibbon et al., 2007, Kimura et al., 2005, Kimura et al., 2007, Kimura et al., 2009, Kimura et al., 2012a, Lam and Sherman, 2007, Lam and Sherman, 2011, Cotillon-Williams et al., 2008, Viviano and Schneider, 2015). In the auditory system auditory cortical areas and thalamic nuclei send topographically organized projections to the auditory sector of the TRN (auditory TRN) that in turn sends topographic projections to the ventral division of the medial geniculate nucleus (MGV) (Kimura et al., 2007). Since cortical and thalamic projections arise from tonotopically organized areas and nuclei (Bordi and LeDoux, 1994a, Rutkowski et al., 2003, Kimura et al., 2005, Polley et al., 2007, Horie et al., 2013, Takemoto et al., 2014, Shiramatsu et al., 2016, Song et al., 2021), the auditory TRN is thought to subserve tonotopy-based modulation of information processing in the MGV (Cotillon-Williams et al., 2008), the first-order auditory thalamic nucleus that relays tonotopically organized tectal auditory inputs to the cortex and TRN (Ledoux et al., 1987, Kimura et al., 2003, Kimura et al., 2009, Kimura et al., 2012a, Storace et al., 2010, Storace et al., 2012, Smith et al., 2012, Bartlett, 2013, Takemoto et al., 2014, Tsukano et al., 2017). Of particular interest is that the putative topography formed by cortical projections from the secondary auditory areas primarily terminating in the medial tier of the TRN is reversed along the dorsoventral neural axis as compared to that formed by those from the primary auditory area primarily terminating in the lateral tier of the TRN (Kimura et al., 2005) or that formed by thalamic projections from the MGV to the TRN (Kimura et al., 2009). As such the effects of inhibitory projections from the auditory TRN on thalamic auditory processing are considered to be complex, comprising influences from these differentially distributed tonotopic inputs. In view of mutual connections among TRN cells (Bazhenov et al., 1999, Shu and McCormick, 2001, Landisman et al., 2002, Sohal and Huguenard, 2003, Zhang and Jones, 2003, Sun et al., 2012, Lee et al., 2014, Lymer et al., 2019), it is further postulated that a given single TRN cell could incorporate tonotopic influences from other cells into its cell activity to exert more complex effects on thalamic cell activity. Features of TRN cell activities related to possible tonotopies inside the TRN are thus considered to represent important aspects of neural processing for modulation of auditory attention and perception. However, at present, it remains unclear whether and how the presumable convergence and interaction of topographically organized cortical and thalamic inputs affect TRN cell activities to form functional organizations as a whole for modulation of auditory processing. The present study examined possible tonotopies in the auditory TRN based on frequencies of sounds (best frequencies), which elicit the most intense auditory response at a given stimulus intensity in TRN cells distributed along the dorsoventral and rostrocaudal neural axes. Experiments were performed on anesthetized rats, using juxta-cellular recording and labeling techniques (Pinault, 1996) that reveal precise single cell activities and locations of cell and terminal field of axonal projection. The present study focused on best frequencies in both early (onset) and late responses, which are, respectively, considered to represent cell activities driven by ascending thalamic inputs and recursive activation of cortical and/or thalamic inputs (Shosaku and Sumitomo, 1983, Cotillon et al., 2000, Kimura and Imbe, 2015) associated with intrinsic cell membrane properties (Avanzini et al., 1989, Llinás and Steriade, 2006, Clemente-Perez et al., 2017).

In conjunction with possible tonotopic organizations, the loop connections of the auditory TRN with cortical areas and thalamic nuclei are thought to compose spatiotemporal frameworks crucial for interaction between preceding and incoming information of sounds of various frequencies, i.e., fundamental neural substrates for auditory attention and perception. Therefore, the present study also focused on single TRN cell activities in interaction between two stimulations of sounds (probe and masker sounds) of different frequencies given with various intervals so as to obtain insights into TRN-mediated gain and/or gate control of auditory temporal processing across sound frequencies. Afterhyperpolarization following supra-threshold cell activity (auditory response), that is intrinsically generated inhibition, is considered to affect subsequent auditory response in repeated sound stimulation (Avanzini et al., 1989, Llinás and Steriade, 2006). In the auditory TRN cellular adaptation to repeated sounds of the same frequency with short intervals abolishes cell activity (Yu et al., 2009). To exclude these conditions, sub-threshold intensities were applied to masker sounds and the effects of masker sounds on subsequent auditory response were examined in supra-threshold cell activities (unit discharges) evoked by probe sounds of frequencies other than those of masker sounds. In the experiments multiple masker sounds of various frequencies were given at random at a specified interval or a single masker sound of a specified frequency was given at various intervals in random order before or after a prove sound.

It has been shown that robust cross-modal alterations of cell activities by visual or somatosensory stimulation take place in the auditory TRN even though visual or somatosensory stimulation does not elicit supra-threshold cell activities (sensory responses) except in a small subset of cells responsive to both auditory and somatosensory stimulations (Kimura, 2014, Kimura, 2017). At present neural substrates for this sub-threshold cross-modal modulation of auditory cell activity are unclear (Halassa and Acsády, 2016, Crabtree, 2018). Intriguing are the effects of comparable sub-threshold intra-modal (auditory) influence on TRN cell activity examined in the present study, which could provide insights into neural mechanism of cross- as well as intra-modal sensory interaction in the TRN.

In the results sound intensity-dependent tonotopic organizations were recognized in both early (onset) and late responses. In the majority of TRN cells sub-threshold masker sound stimulation altered early and/or late responses to probe sound stimulation with regard to response magnitude, latency, and/or burst spiking properties. The majority of alterations in response magnitude were attenuation as recognized in cross-modal modulation (Kimura, 2014, Kimura, 2017). Late responses were affected by masker sounds given either before or after early responses. These robust and complex interactions across sound frequencies suggest that TRN cells, which are embedded in tonotopic organizations structured by ascending and recursive activations in combination with intrinsic cell membrane properties, incorporate various sound information into their temporal activities to modulate thalamic auditory processing. The findings are also considered to signify features of neural substrates for cross-modal modulation of cell activities in the auditory TRN (Kimura, 2014, Kimura, 2017) to which cortical and thalamic excitatory inputs of multiple sensory modalities converge (Yu et al., 2011, Kimura et al., 2012a) like those of multiple sound frequencies for intra-modal modulation.

Section snippets

Animals and surgical procedures

Experiments were performed on 41 male adult (age, 8–10 weeks) Wistar rats (Kiwa Laboratory Animal, Wakayama, Japan) weighing 317–367 g (mean, 340 g) in accordance with the institutional animal care and use protocol approved by the Animal Research Committee of Wakayama Medical University, which conforms to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

After initial induction of an anesthetized state by an intraperitoneal (i.p.) bolus injection of

Results

Cell activities were recorded from 114 TRN cells in 41 animals. Locations of 83 cells in the TRN were histologically verified by labeling of cell body. The other cells (n = 31), which could not be labeled, were confirmed to be located in the TRN based on the depth of recording site from the cortical surface, the locations of labeled cells in the same track of recording electrode, and the features of intense burst spiking characteristically observed in TRN cells (Llinás and Steriade, 2006,

Discussion

The results indicate sound intensity-dependent tonotopic organizations and tonotopy-related robust alterations of cell activities (onset and recurrent late auditory responses) across sound frequencies. The major findings are summarized as follows. Tonotopic organizations for onset and late responses are recognized in cell (in the TRN) and terminal field locations (in the MGV) along the dorsoventral, rostrocaudal and/or mediolateral neural axis (Table 1, Table 2, Table 3, Table 4, Table 5, Table

Acknowledgements

This work was supported by JSPS KAKENHI Grant Numbers JP17K07081. The author declares no competing financial interests.

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