Page 38 - Spring2022

EARLY AUDITORY EXPERIENCE
What Are Subplate Neurons Listening to?
Given that sounds can shape the early established circuits, it seems natural to identify which sounds are likely to influence subplate circuits in both humans and altricial animals. In humans, external sounds will be attenuated and filtered by the womb (Gerhardt et al., 1990) and the mother will be the dominant source of sounds. Sources generated by the mother will include breathing, heart- beat, digestive noises, and vocalizations. A distinguishing feature between these sounds is that the first three are ongoing and have relatively constant spectral content, whereas speech is more rare and variable.
Given that developing synapses show high rates of adap- tation and that young neurons do not sustain high firing rates, responses to ongoing stimuli likely adapt quickly. In contrast, natural speech has a varying frequency con- tent, is irregular, and is likely to produce less adaptation. Therefore, it is likely that intermittent speech sounds will cause more subplate activity than background sounds. Similarly, external sounds such as other voices or music can be transmitted to the fetus but will be attenuated and filtered. Thus, rare lower frequency sounds will be most effective in activating subplate neurons (Hepper and Sha- hidullah, 1994).
In animals, the situation is similar, but because the ear canals are closed, maternal vocalizations are attenuated. Moreover, given that pups are outside the womb, other sources of sound are present. Some major potential sound sources are self-generated vocalizations and vocalizations of conspecifics close by in the nest. Thus, it is intriguing to speculate that self-generated sound stimuli could aid in the development of the auditory system in altricial animals. Such a scenario is not too far-fetched because elegant work in ducklings has shown a role for self-vocal- izations in auditory development (Gottlieb, 1971).
These considerations also apply to the auditory environ- ment in the NICU because premature infants are suddenly exposed to a very different auditory environment than they had experienced in the womb. High-frequency sounds are not attenuated outside the womb and can potentially drive neural activity. Therefore, care should be taken to replicate the fetal environment by attenuating such sounds. Furthermore, providing rare, speech-like sounds such as recordings of the mother might be of use.
Damage of Subplate Neurons Might Cause Developmental Abnormalities
and Sensory Dysfunctions
Given their key location and early development, it should be of no surprise that damage of the subplate neurons due to exposure to drugs or injury leads to developmental abnormalities, including those associated with sensory- processing deficits. For example, lesioning subplate neurons prevents the topographic and functional matu- ration in layer 4 (Kanold and Luhmann, 2010) and leads to altered large-scale activity changes in the brain (Tolner et al., 2012), suggesting that the altered brain activ- ity observed in infants could be indicative of subplate damage or lesions. Moreover, neonatal hypoxia-ischemia, which in humans is linked to a variety of neurodevel- opmental disorders, leads to subplate hyperconnectivity (Sheikh et al., 2019). Subplate abnormalities are also seen in rodent models of autism spectrum disorder (ASD) (Nagode et al., 2017). Thus, sensory-processing deficits in multiple neurodevelopmental disorders could be the consequence of early subplate damage that prevents the maturation of cortical sensory processing.
Outlook
If and how the early sound experience can shape our auditory system has long been debated. Studies of early development of the auditory cortex in animals have shown that sound-evoked activity is present much ear- lier than previously assumed and that an early sensory experience can leave a long-lasting trace. It remains to be tested if such early exposure can influence the further development of the cortex and could thereby promote language or musical learning at infant ages.
The considerations discussed draw almost exclu- sively from nonhuman animal studies. The subplate is expanded and more compartmentalized in primates than in rodents (Molnar and Clowry, 2012), indicating that subplate size might scale with brain complexity. It is an open question if humans contain specialized subplate neurons or if human brains are enriched in certain sub- plate subpopulations.
Acknowledgments
This work was supported by National Institutes of Health Grant R01-DC-009607. I thank Zara Kanold-Tso for help with Figure 1. Also, I thank both past and present
38 Acoustics Today • Spring 2022