Page 35 - Spring2022

Subplate neurons are the earliest born cortical excitatory neurons and reside at the bottom of the cortex (Kostovic and Rakic, 1980). Moreover, subplate neurons, in con- trast to other cortical neurons, mostly disappear during development (Luskin and Shatz, 1985) and form a tran- sient population of deep neurons.
There is also another group of early-generated tran- sient neurons on the outer margin of the cortex; hence, although the adult cortex contains six layers, the develop- ing cortex contains additional largely transient neuronal layers at its deeper and outer margins (Molnár et al., 2020). The sequential generation of neurons is important for understanding the varying effects of developmental insults and injuries. Insults at younger ages will most directly affect early-born deep neurons, whereas insults at later ages will influence both superficial and deep neurons. This means that because deep and superficial neurons perform different functions, the same insults at different times can have distinct functional consequences.
Subplate Neurons Are the First
Cortical Cells to Respond to Sounds and the Substrate of Early Topography
Neurons grow projections, called axons, and communi- cate via specialized structures called synapses, thereby forming neural circuits. The earliest generated transient neuronal layers are also the site of the early establishment of cortical synapses (Kostovic and Molliver, 1974). In
adults, the input layer of the ACtx, layer 4, receives direct synaptic inputs from the MGB (Figure 2A) (Budinger and Kanold, 2018). This direct pathway is crucial for transmitting sound-evoked activity from the inner ear to the ACtx and thus is essential for auditory process- ing. In early development, this direct connection does not exist. Instead, MGB neurons first form synapses with subplate neurons (Kanold and Luhmann, 2010), and MGB axons remain constricted to the subplate for a period before growing to their eventual target in layer 4. Consistent with the early MGB inputs to the subplate, recordings in young animals have shown that subplate neurons respond to sound before ACtx layer 4 neurons (Wess et al., 2017).
During this time period, subplate neurons themselves project to the ACtx layer 4 (Zhao et al., 2009); thus subplate neurons form an essential relay for sound infor- mation to reach layer 4 and beyond (Figure 2A) (Wess et al., 2017). The direct transmission between the MGB and the ACtx layer 4 and thus the adult-like pattern emerge after ear opening (Barkat et al., 2011) and subplate neu- rons disappear during subsequent development (Kanold and Luhmann, 2010). These results also suggest that the early sound-evoked responses detected in human babies are due to subplate activation.
Although the ACtx contains the tonotopic map in adults, in early development, there is no map (Figures 1A and 2B).
Figure 2. A: subplate neurons relay ascending MGB activity to layer 4 in development, whereas in adults, the MGB directly activates layer 4. B: model of topographic mapping of frequency preference (colors) by ordered projections from the MGB to ACtx layer 4. Left: old model suggests that the adult pattern emerges from initially unordered and unrefined projections to layer 4. Right: new model suggests that topographic organization emerges first by projections to the subplate and later in layer 4. Dashed line, maturing connection.
Spring 2022 • Acoustics Today 35