Subplate neurons are the first cortical neurons to respond to sensory stimuli

Abstract

In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to layer 4 as well as the ear and eye opening. In developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons deep in the developing white matter. We investigated if subplate neurons respond to sensory stimuli. Using electrophysiological recordings in young ferrets, we show that auditory cortex neurons respond to sound at very young ages, even before the opening of the ears. Single unit recordings showed that auditory responses emerged first in cortical subplate neurons. Subsequently, responses appeared in the future thalamocortical input layer 4, and sound-evoked spike latencies were longer in layer 4 than in subplate, consistent with the known relay of thalamic information to layer 4 by subplate neurons. Electrode array recordings show that early auditory responses demonstrate a nascent topographic organization, suggesting that topographic maps emerge before the onset of spiking responses in layer 4. Together our results show that sound-evoked activity and topographic organization of the cortex emerge earlier and in a different layer than previously thought. Thus, early sound experience can activate and potentially sculpt subplate circuits before permanent thalamocortical circuits to layer 4 are present, and disruption of this early sensory activity could be utilized for early diagnosis of developmental disorders.

Transient coupling between subplate and subgranular layers to L1 neurons before and during the critical period

“…Recent studies have suggested that L1 contains topographic maps (Takesian et al, 2018), which might aid in shaping maps in L4. Since early topographic maps develop in the subplate (Wess et al, 2017), our results here suggest that such maps may result from subplate projections to L1. Studies in cat have implicated subplate neurons for normal critical period plasticity (Kanold and Shatz, 2006).…”

“…Thalamic input to the developing cortex first targets neurons deep in the cortex, the subplate neurons (Friauf and Shatz, 1991;Hanganu et al, 2002;Higashi et al, 2005;Kanold and Luhmann, 2010;Zhao et al, 2009) which are the first cortical neurons to respond to sensory stimuli and to show topographic organization (Wess et al, 2017). Subplate neurons send axonal projections to L4 as well as other layers, and excite both excitatory and inhibitory L4 neurons (Deng et al, 2017;Viswanathan et al, 2017;Zhao et al, 2009).…”

“…The underlying circuit mechanisms for the enhanced capacity for plasticity during the critical period have remained unclear. Developing thalamocortical projections first target subplate neurons (Friauf and Shatz, 1991;Hanganu et al, 2002;Higashi et al, 2002;Zhao et al, 2009) and accordingly cortical sensory responses are first observed in subplate neurons Kanold and Luhmann, 2010;Wess et al, 2017). Subplate neurons project to layer 4 (L4) but also to more superficial layers, such as layer 1 (L1) (Deng et al, 2017;Kanold and Luhmann, 2010;Viswanathan et al, 2017;Zhao et al, 2009).…”

Cortical responses to tactile stimuli in preterm infants

“…Prior experimental work on rodent models has indicated a key role of subplate in SER generation, and changes in subplate‐cortex interaction likely reflect on the developmental characteristics of SERs (Luhmann & Khazipov, ; Luhmann, Kirischuk, & Kilb, ). For instance, subplate ablation will abolish both endogenous and sensory evoked spindle burst activity (Tolner, Sheikh, Yukin, Kaila, & Kanold, ), and subplate neurons are reactive to sensory stimuli before other the reaction becomes visible in cortical neurons (Wess et al, ). Subplate neuronal networks provide hence a relay between thalamus and cortex, and the subplate neurons allow coordination of cortical network ensembles, which is believed to provide key guidance for early cortical organization (Luhmann et al, ).…”

“…Studies on both animal (Colonnese et al, ; Hanganu, Ben‐Ari, & Khazipov, ; Khazipov et al, ; Minlebaev, Ben‐Ari, & Khazipov, ) and human infants (Hrbek et al, ; Milh et al, ; Vanhatalo, Jousmaki, Andersson, & Metsaranta, ) have shown how cortical reaction to sensory stimulation (somatosensory evoked reaction/response, SER) in a preterm brain is substantially different from that of a term infant or an older child. The earliest cortical reactions to sensory stimulation are very large, they take place in the subplate and deeper cortical layers (Luhmann & Khazipov, ; Wess, Isaiah, Watkins, & Kanold, ), and they can be readily observed at individual response level in the human neonate (Hrbek et al, ; Milh et al, ; Vanhatalo et al, ). During the preterm period corresponding to the last trimester of pregnancy, these responses will gradually relocate into cortex proper, diminish in size and eventually become so small that averaging techniques are needed for their detection (Hrbek et al, ).…”