Scientific Understanding of Consciousness
Visual Area Distinctions driven by Geniculocortical Input
Science 7 June 2013: Vol. 340 no. 6137 pp. 1239-1242
Geniculocortical Input Drives Genetic Distinctions Between Primary and Higher-Order Visual Areas
Shen-Ju Chou, Zoila Babot, Axel Leingärtner, Michele Studer, Yasushi Nakagawa, Dennis D. M. O'Leary
1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
2Institute of Biology Valrose, INSERM, Nice, France.
Studies of area patterning of the neocortex have focused on primary areas, concluding that the primary visual area, V1, is specified by transcription factors (TFs) expressed by progenitors. Mechanisms that determine higher-order visual areas (VHO) and distinguish them from V1 are unknown. We demonstrated a requirement for thalamocortical axon (TCA) input by genetically deleting geniculocortical TCAs and showed that they drive differentiation of patterned gene expression that distinguishes V1 and VHO. Our findings suggest a multistage process for area patterning: TFs expressed by progenitors specify an occipital visual cortical field that differentiates into V1 and VHO; this latter phase requires geniculocortical TCA input to the nascent V1 that determines genetic distinctions between V1 and VHO for all layers and ultimately determines their area-specific functional properties.
The neocortex is patterned into functionally distinct fields that include primary sensory areas, which receive modality-specific sensory input from thalamocortical axons (TCAs) that originate from the principal sensory nuclei of the dorsal thalamus (dTh), and higher-order sensory areas that are connected with the primary areas through intracortical projections. Studies of mechanisms that pattern the neocortex into areas, known as arealization, have focused on primary areas and have led to the prevailing model that genetic mechanisms intrinsic to the neocortex are predominant in arealization. Transcription factors (TFs) expressed in neocortical progenitors determine the size and position of primary areas and regulate guidance information that governs the area-specific targeting of TCAs. However, roles for TCAs in arealization remain vague and important features of arealization, such as differential gene expression in the embryonic neocortex that relates to nascent areas, develop independently of TCA input.
Higher-order areas outnumber primary areas by roughly 10-fold; for example, in mouse, nine higher-order visual areas (VHO) are positioned around the primary visual area (V1) within the occipital neocortex. However, mechanisms that specify and regulate differentiation of the particular properties of higher-order areas and distinguish them from primary areas have yet to be explored.
The geniculocortical TCA projection that relays visual information from the eyes selectively to V1.
To visualize TCA projections in the cortex, we first used serotonin [5-hydroxytryptamine (5-HT)] immunostaining on tangential sections of flattened P7 cortices.
We have shown a prominent role for TCA input and redefined the role of intrinsic genetic regulation of the differentiation of higher-order sensory areas from primary sensory areas. We selectively deleted geniculocortical TCA input to V1 early in postnatal development to accomplish two goals: (i) to assess the requirement of geniculocortical TCA input for the differentiation of genetic profiles that distinguish V1 from VHO and establish their specific functional properties; and (ii) to isolate the function of intrinsic genetic mechanisms to assess their role relative to geniculocortical TCAs in the specification and differentiation of V1 and VHO. Isolating in cKO mice the function of intrinsic genetic mechanisms in patterning V1 and VHO redefined their roles in arealization and showed that they specify an occipital visual cortical field that has a similar genetic profile over its extent. Geniculocortical TCA input is required postnatally to differentiate the visual cortical field into V1 and VHO and establish the genetic profiles that delineate and distinguish them. Regardless of whether in WT mice the gene and protein markers were more highly expressed in V1 than VHO, or vice versa, they exhibited significant changes in their patterned expression in cKO mice in which geniculocortical TCA input was deleted, resulting in a uniform intermediate level of expression across the occipital visual cortical field that would normally differentiate into V1 and VHO. The change from patterned to uniform expression occurred through bidirectional changes in expression, with both down-regulation of expression in V1 and up-regulation in VHO, or vice versa, to produce intermediate expression levels across the occipital visual cortical field despite the selective targeting in WT mice of geniculocortical TCAs to only part of the occipital visual cortical field; i.e., the nascent V1. These changes in patterned gene expression occurred not only in the primary TCA target layer 4, but also in layers 2, 3, and 5, which receive little or no direct TCA input.
Our findings require a revision of the prevailing model of arealization and indicate a working model with distinct stages: Intrinsic genetic mechanisms specify an occipital visual cortical field with a relatively uniform genetic profile, followed by its differentiation into V1 and VHO driven by geniculocortical TCA input targeted selectively to the nascent V1. This multistage process of arealization creates the hierarchical cortical organization of primary and higher-order visual areas that is required for proper visual perception and behavior.
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