A Parallel Tonotopically Arranged Thalamocortical Circuit for Sound Processing

Neurology Medicine
thalamocortical circuit sound processing tonotopic arrangement mouse study neuroscience

In the mammalian brain, auditory perception relies on the transmission of information from the thalamus to the cortex. For a long time, the medial geniculate body (MGB) has been considered the primary hub of the auditory thalamus, responsible for transmitting sound signals to the auditory cortex (Auc). However, whether other thalamic inputs also participate in this process remains an unsolved mystery. To address this question, researchers explored whether a region in the thalamus called the ventromedial nucleus (VM), particularly its basal part (basal region of the ventromedial nucleus, BVM), is involved in auditory information processing.

Source of the Paper

This paper was co-authored by Zhikai Zhao, Xiaojing Tang, Yiheng Chen, and others from multiple research institutions, including Chongqing University, Third Military Medical University, and Guangxi University. The study was published on June 18, 2025, in the journal Neuron, titled A Parallel Tonotopically Arranged Thalamocortical Circuit for Sound Processing.

Research Process

1. Identifying BVM Projections to the Auditory Cortex

The study first used fluorescent retrograde tracing technology, injecting cholera toxin B (CTB) into the auditory cortex of mice. They discovered that a large number of neurons in the BVM region project to the auditory cortex. These neurons are primarily located in the basal part of the thalamus, and these projections exhibit frequency tuning characteristics, matching the tonotopic map of the auditory cortex.

2. Functional Validation of BVM Projections

To validate the function of BVM projections, researchers inhibited the activity of BVM neurons using chemogenetics. The results showed that inhibiting BVM projections significantly reduced the auditory cortex neurons’ response to sound and impaired the mice’s performance in sound frequency discrimination tasks. Particularly in tasks involving close frequency sounds (e.g., 0.25-octave intervals), the mice’s performance declined significantly.

3. Frequency Tuning Characteristics of BVM Projections

Using two-photon calcium imaging technology, researchers recorded the activity of BVM axons in the auditory cortex. The results revealed that BVM axons exhibit strong tuning characteristics to specific sound frequencies, and these tuning characteristics align with the tonotopic map of the auditory cortex. This indicates that BVM projections have frequency selectivity in auditory information processing.

4. Synaptic Targets of BVM Projections

To determine the synaptic targets of BVM projections, researchers used optogenetics and whole-cell patch-clamp recording techniques. They found that BVM axons primarily form excitatory synaptic connections with neuron-derived neurotrophic factor-positive (NDNF+) interneurons in layer 1 of the auditory cortex. These interneurons play a crucial role in regulating cortical neuron activity.

5. Behavioral Significance of BVM Projections

Finally, researchers further validated the function of BVM projections through behavioral experiments. They found that inhibiting BVM neuron activity significantly reduced the mice’s performance in auditory discrimination tasks, particularly in tasks involving close frequency sounds. This demonstrates the critical role of BVM projections in auditory information processing.

Key Findings

  1. BVM Projections to the Auditory Cortex: BVM neurons project to the auditory cortex, and these projections exhibit frequency tuning characteristics that align with the tonotopic map of the auditory cortex.
  2. Function of BVM Projections: Inhibiting BVM projections significantly reduces auditory cortex neurons’ response to sound and impairs mice’s performance in sound frequency discrimination tasks.
  3. Frequency Tuning Characteristics of BVM Projections: BVM axons exhibit strong tuning characteristics to specific sound frequencies, and these tuning characteristics align with the tonotopic map of the auditory cortex.
  4. Synaptic Targets of BVM Projections: BVM axons primarily form excitatory synaptic connections with NDNF+ interneurons in layer 1 of the auditory cortex.
  5. Behavioral Significance of BVM Projections: Inhibiting BVM neuron activity significantly reduces mice’s performance in auditory discrimination tasks, particularly in tasks involving close frequency sounds.

Conclusion

This study reveals a novel thalamocortical pathway, namely BVM projections to the auditory cortex. This pathway operates in parallel to the classic MGB/Auc pathway, jointly participating in auditory information processing. BVM projections exhibit frequency tuning characteristics and primarily form excitatory synaptic connections with NDNF+ interneurons in layer 1 of the auditory cortex. Inhibiting BVM projections significantly reduces auditory cortex neurons’ response to sound and impairs mice’s performance in sound frequency discrimination tasks. This discovery not only expands our understanding of auditory information processing mechanisms but also provides new insights for the treatment of auditory-related disorders.

Highlights of the Study

  1. Discovery of a Novel Thalamocortical Pathway: This study is the first to reveal BVM projections to the auditory cortex, expanding our understanding of auditory information processing mechanisms.
  2. Frequency Tuning Characteristics: BVM projections exhibit frequency tuning characteristics that align with the tonotopic map of the auditory cortex, indicating their frequency selectivity in auditory information processing.
  3. Identification of Synaptic Targets: BVM axons primarily form excitatory synaptic connections with NDNF+ interneurons in layer 1 of the auditory cortex, revealing their role in regulating cortical neuron activity.
  4. Behavioral Validation: Inhibiting BVM projections significantly reduces mice’s performance in sound frequency discrimination tasks, particularly in tasks involving close frequency sounds, validating their behavioral significance.

Significance and Value

This study not only highlights the critical role of BVM projections to the auditory cortex in auditory information processing but also provides new insights for the treatment of auditory-related disorders. For example, modulating the activity of BVM projections may improve auditory perception in patients with hearing impairments. Additionally, this study offers new perspectives for understanding the processing mechanisms of other sensory information.

Other Valuable Information

The study employed various advanced techniques, including fluorescent retrograde tracing, chemogenetics, two-photon calcium imaging, optogenetics, and whole-cell patch-clamp recording. The application of these technologies not only enhanced the precision and reliability of the research but also provided technical references for future related studies.