Page 36 - Spring2022

EARLY AUDITORY EXPERIENCE
Classic experiments in the visual system have shown that topographic order emerges during development because of a refinement process of the thalamic projections to corti- cal layer 4 (LeVay et al., 1978). The development from the MGB to layer 4 of the ACtx is also thought to undergo such refinement (Figure 2B, left) (Razak et al., 2009). However, recordings in young animals showed a topographic orga- nization of sound-evoked responses in the subplate at ages before layer 4 neurons responded to sound (Wess et al., 2017). Thus, topographic maps emerge in the subplate and not in layer 4 and also earlier than previously appreciated (Wess et al., 2017).
These observations suggested a new model of the devel- opment of cortical topographic maps; maps might be established in the subplate and these maps might later be transferred into layer 4 by the projections from the subplate to layer 4 (Figure 2B, right). Although the devel- opment of MGB projections to the subplate and then to layer 4 is sequential, this sequential nature is not a general rule across the auditory-processing hierarchy. Hence, one can speculate that the initial period when MGB fibers are present in the subplate serves a particular developmental purpose, namely, developing a functional scaffold aiding the development of cortical organization. In this model, building an initial sketch, or scaffold, of the topographic map in parallel with the generation of the cortical layers could enable faster development of sensory cortical func- tion than serial layer generation and map development.
The Role of Neural Activity and Early Sen- sory Experience on Cortical Development Neural activity plays a big role in shaping brain circuits. However, the origin of this activity and its nature change during development. At the earliest stages of development, a large part of the neural activity observed in the brain appears to be overtly “spontaneous,” meaning not occur- ring in response to an external sensory stimulus (Khazipov and Luhmann, 2006). Later in development, neural activity driven by sensory stimuli such as sounds becomes domi- nant. One important source of early spontaneous activity is the cochlea (Tritsch et al., 2007), which produces sponta- neous activity before the onset of sensory transduction and ear opening, although it wanes after ear opening. Work in developing rodents has shown that cochlea-generated spontaneous activity propagates all the way to the ACtx (Babola et al., 2018). The peripheral generated spontane- ous activity patterns can be thought of as test patterns that
prime the downstream circuits for the onset of the sensory experience and play a key role in sculpting nascent circuits before the onset of sensory functions.
The effects of the sensory experience during the periods where peripheral spontaneous activity is present have only recently been started to be studied. This is because it had been assumed that animals did not hear before ear opening. But because the ACtx can show sound-evoked responses before the ears open (Wess et al., 2017); this indicated the potential for an effect of the sound experi- ence on ACtx circuits.
Subplate neurons also receive inputs from the developing cortical neurons (Viswanathan et al., 2012). The topology of these circuits can be studied in rodent brain slice prepara- tions (Figure 3A) and allows for the study of circuit changes after manipulations. Studies in genetically deaf mice, for example, such as those deficient in mechanotransduction (Meng et al., 2021) or synaptic function (Mukherjee et al., 2021), revealed that their subplate neurons receive inputs
Figure 3. A: subplate neurons receive intracortical inputs, and early deafness leads to hyperconnectivity of subplate neurons. Images show the density of inputs from each cortical location to subplate in mice. In deaf mice, connections to subplate neurons arise from more neurons. Adapted from Meng et al. (2021). B: the 3 phases of early auditory development. Gray, stages of hearing. SP, subplate; P11 and P18, postnatal days 11 and 18, respectively.
36 Acoustics Today • Spring 2022