Early sensory experience influences the development of multisensory thalamocortical and intracortical connections of primary sensory cortices

Abstract

The nervous system integrates information from multiple senses. This multisensory integration already occurs in primary sensory cortices via direct thalamocortical and corticocortical connections across modalities. In humans, sensory loss from birth results in functional recruitment of the deprived cortical territory by the spared senses but the underlying circuit changes are not well known. Using tracer injections into primary auditory, somatosensory, and visual cortex within the first postnatal month of life in a rodent model (Mongolian gerbil) we show that multisensory thalamocortical connections emerge before corticocortical connections but mostly disappear during development. Early auditory, somatosensory, or visual deprivation increases multisensory connections via axonal reorganization processes mediated by non-lemniscal thalamic nuclei and the primary areas themselves. Functional single-photon emission computed tomography of regional cerebral blood flow reveals altered stimulus-induced activity and higher functional connectivity specifically between primary areas in deprived animals. Together, we show that intracortical multisensory connections are formed as a consequence of sensory-driven multisensory thalamocortical activity and that spared senses functionally recruit deprived cortical areas by an altered development of sensory thalamocortical and corticocortical connections. The functional-anatomical changes after early sensory deprivation have translational implications for the therapy of developmental hearing loss, blindness, and sensory paralysis and might also underlie developmental synesthesia.

Self-generated whisker movements drive state-dependent sensory input to developing barrel cortex

“…It is difficult to imagine how spontaneous neural activity alone could account for the exquisite mapping that develops between body and brain. As is well known, peripheral manipulations of the visual, auditory, and somatosensory systems produce marked changes in cortical representations [21][22][23][24]. Nowhere is this more clear than in developing barrel cortex, in which whisker removal and peripherally expressed genetic manipulations reliably alter its structural organization (see [25] for review).…”

“…Whereas some groups posit that selfgenerated movements, particularly twitches, drive critical early activity in somatosensory 7 cortex [5,9], others explicitly state that the sensory feedback from movements is not necessary, instead positing that spontaneous neural activity within the brain is alone sufficient for typical development [3,4].It is difficult to imagine how spontaneous neural activity alone could account for the exquisite mapping that develops between body and brain. As is well known, peripheral manipulations of the visual, auditory, and somatosensory systems produce marked changes in cortical representations [21][22][23][24]. Nowhere is this more clear than in developing barrel cortex, in which whisker removal and peripherally expressed genetic manipulations reliably alter its structural organization (see [25] for review).Nonetheless, recent reports appear to show that sensory feedback from movements is unrelated to ongoing neural activity within the somatosensory system [3,4].…”

Effects of enucleation on the direct reciprocal corticocortical connections between primary visual and somatosensory cortices of the mouse

“…Conversely, early sustained sensory deprivation enhanced direct corticocortical projections between primary sensory cortices were reported in subadult (P28) gerbils (Henschke et al, 2017). Corticocortical connections are expanded in enucleated opossums (Karlen et al, 2006), suggesting that perhaps in marsupials the removal of the eyes at a very early stage of development compared to rodents, might alter cortical connections to a greater extent.…”

“…(Magrou et al, 2017). Similarly, after early and sustained sensory deprivation in gerbils, many projections between primary sensory cortices maintained more numerous supragranular layers projection neurons, indicating that they 6 retain a less mature laminar feedforward-like pattern (Henschke et al, 2017) and that afferent sensory activity is required for the establishment of the normal connectivity patterns. The quantitative effects of neonatal bilateral enucleation on the reciprocal corticocortical connections between the primary visual and somatosensory cortices were studied here in adult mice to better understand how afferent sensory activity affects their reciprocal asymmetric connectivity and relative structure.…”

Alterations in cortical and thalamic connections of somatosensory cortex following early loss of vision

“…In these animals, connections between the primary visual (V1) and somatosensory (S1) areas were altered and functional multisensory enhancement between these fields was absent (Sieben et al, 2015). Alterations in both thalamocortical and corticocortical connections of primary sensory fields have also been observed with postnatal sensory loss in gerbils (Henschke et al, 2018), and in the cortical connections of mice that were bilaterally enucleated at birth (Abbott, Kozanian, & Huffman, 2015). Thus, even after the onset of spontaneous activity and the establishment of thalamocortical connections, loss of sensory-driven input can have a rather large effect on the cortical connections of both the targeted and nontargeted primary sensory fields as well as their thalamocortical connections.…”