Prenatal activity from thalamic neurons governs the emergence of functional cortical maps in mice

Abstract

The mammalian brain’s somatosensory cortex is a topographic map of the body’s sensory experience. In mice, cortical barrels reflect whisker input. We asked whether these cortical structures require sensory input to develop or are driven by intrinsic activity. Thalamocortical columns, connecting the thalamus to the cortex, emerge before sensory input and concur with calcium waves in the embryonic thalamus. We show that the columnar organization of the thalamocortical somatotopic map exists in the mouse embryo before sensory input, thus linking spontaneous embryonic thalamic activity to somatosensory map formation. Without thalamic calcium waves, cortical circuits become hyperexcitable, columnar and barrel organization does not emerge, and the somatosensory map lacks anatomical and functional structure. Thus, a self-organized protomap in the embryonic thalamus drives the functional assembly of murine thalamocortical sensory circuits.

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

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Cortical development is an activity-dependent process [1][2][3]. Regarding the role of activity in developing somatosensory cortex, one persistent debate concerns the importance of sensory feedback from self-generated movements.

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“…Regarding the role of activity in developing somatosensory cortex, one persistent debate concerns the importance of sensory feedback from self-generated movements. Specifically, recent studies claim that cortical activity is generated intrinsically, independent of movement [3,4]. However, other studies claim that behavioral state moderates the relationship between movement and cortical activity [5][6][7].…”

“…In the somatosensory system, however, the debate continues about the importance of peripheral sensory input for cortical development. 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].…”

“…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]. We suspected that these contradictory findings resulted from the use of methods that are inadequate for detecting movement-related neural activity.…”

“…Interestingly, these values are largely consistent with previous studies in which researchers blocked sensory feedback from the whiskers [11] or limbs [9,12] and observed 50-75% decreases in the rate of spindle bursts. The current findings show that, by carefully attending to self-generated movement and behavioral state in intact animals, we can accurately assess the relationships between behavior and early brain activity.The distinction between sensory input and "intrinsic activity" as contributors to cortical development was extended recently to the late prenatal period in mice (see [3]). Asserting that this is a period "before sensory input," the authors concluded that sensory input cannot play a role in the observed cortical map structure.…”