Page 34 - Spring2022

EARLY AUDITORY EXPERIENCE
between the different processing stages (Hackett et al., 2011). For example, cells in the low-frequency region of the MGB (Figure 1A, blue) project to one end of the ACtx (Figure 1A, blue) while cells in the high-frequency region of the MGB (Figure 1A, red) project to the other end of the ACtx (Figure 1A, red).
The Development of “Hearing”
The development of the auditory system, and especially the ACtx, is a protracted process starting prenatally. Extensive work in animals has shown that the develop- mental process requires a complex interplay of genetic programs, spontaneous and sensory-driven neural activ- ity; so both “nature” and “nurture” are heavily involved (Goodrich and Kanold, 2020).
The general sequence of processing stages between the ear and the ACtx is also present in development (Goodrich and Kanold, 2020), with one important exception. In early development, there is an additional specialized population of neurons, subplate neurons, that are present in the ACtx in early development before the MGB is con- nected to the ACtx (Figure 1B). These subplate neurons form early relay circuits connecting the MGB with the input layer of the ACtx (layer 4) and form a specialized developmental structure that provides a functional scaf- fold for the permanent wiring of the cortex. This review focuses on these specialized circuits, the events that can shape their function, and ways by which these circuits can influence later ACtx function.
In humans, physiological or neural responses to sound emerge around the end of the second trimester. A funda- mental concept to define is the onset of hearing. Hearing has both sensory-processing and cognitive components because attention-based mechanisms can amplify or sup- press sound-evoked responses, such as when ignoring background noises or attending to a particular instru- ment in an orchestra. For the purposes of this review, hearing means the onset of auditory processing and does not cover the cognitive aspects.
Auditory-processing development starts with the matura- tion of the cochlea and requires the neural transmission of sound-evoked neural activity to the brainstem and more central structures such as the ACtx. External sounds can be transmitted to the fetus but are attenuated by the womb, whereas sounds generated by the mother can be enhanced
by conduction from the larynx to the body (Richards et al., 1992). Accordingly, the fetal environment is rich in potential auditory stimuli. Fetal movements in response to externally generated low-sound frequencies can be detected midgestation, at about the 19th GW, whereas responses to higher frequencies emerge later (Hepper and Shahidullah, 1994). Consequently, it can be reasoned that the human inner ear and, at least, the brainstem circuits must be functional at these ages, albeit likely not mature.
The more detailed development of auditory processing has been studied in animal models such as mice and fer- rets that are born in a more immature state (altricial). Much of the development that happens in the womb in humans happens after birth in altricial animals. Further- more, altricial animals undergo a major transition in their hearing in that they are born with closed ear canals that attenuate sounds and that open postnatally. More- over, a major difference between altricial animals and humans is that the early sound environment in humans will be dominated by maternal sounds, whereas maternal sounds will be attenuated in altricial animals.
Indeed, although ear opening in altricial animals is some- times called the “onset of hearing,” data from multiple altricial species such as ferrets (Wess et al., 2017) and mice (Meng et al., 2020) show that auditory responses are present even at the level of ACtx at time periods when the ears are closed. Although sound-evoked responses can be recorded, it should be emphasized that these responses are not mature, and therefore neurons in young animals do encode sensory stimuli as robustly as the adult does. Together, these studies give us rough estimates of when peripheral sounds drive neural activity in the auditory system, but due to experimental limitations, it is possible that even earlier responses exist.
Formation of the Auditory Cortex and Its Connections
The ACtx consists of six layers of neurons that are dis- tinguished by differences in neuronal cell shape and connectivity (Figure 1A) (Budinger and Kanold, 2018). The major group of cortical neurons, excitatory neurons, are generated in the bottom of the cortex, and with each round of cell generation, a different layer is built (Figure 1B). Newborn neurons will move past older mature neu- rons and stack on top of each other; therefore, the cortex is built from the bottom up.
34 Acoustics Today • Spring 2022