Cortical GABAergic interneurons in cross-modal plasticity following early blindness

Abstract

Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA) play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field.

Figure 1

Primary cortical areas in three species of mammals (i.e., Mouse, Ghost Bat and Opossum) that have approximately the same size cortical sheet, but different amounts of cortex allowed to different sensory modality (S: Somatosensory system, A: Auditory system and V: Visual system), related to use of particular sensory receptor arrays. In the mouse (top left), which relies heavily on tactile inputs from the whiskers for survival, the somatosensory cortex (S) is enlarged, compared with the ghost bat (bottom left) and normal opossum (top right). The auditory cortex (A) in the neocortex of the echolocating ghost bat is expanded, while the visual area (V) and S is relatively small. Similarly, the cortex of the highly visual opossum have a dominant visual cortex. Finally, for example, in the enucleated at birth opossum (bottom right) the V cortex becomes smaller and is recruited by the A and S modalities. Similarity in relative location of sensory cortical fields in all these mammals suggests that the topographic organization and overall pattern of thalamocortical projections of the brain is constrained by developmental mechanisms. Conversely, the differences in size, shape, and detailed organization of sensory cortical fields indicate that input from the periphery is a crucial factor in guiding many of the details of organization of the neocortex. Rostral is to the left and medial is up. Scale bar = 1 mm. Adapted from Kahn and Krubitzer, 2002 [48].

Figure 2

Hamster models of cross-modal plasticity. Photomicrographs examples of normal (a), SC lesioned (b) and enucleated (c) hamsters. Column a: top figure showing normal hamster brain with intact superior colliculus and optic chiasm (black arrow heads). At the bottom a simplified schematic representation of the normal visual and auditory pathways. Column b: At the top Superior colliculus (SC) lesioned hamster brain were the SC and optic chiasm are atrophied (black arrow heads). Underneath, diagrams showing the new ectopic retinal projections to the LP in the SC lesioned and to the MG in the SC + ICb lesioned animals. Column c: Enucleated case with an evident SC but complete absence of optic nerves and optic chiasm (arrows). Bottom diagram illustrating the new ectopic auditory projections between the IC and the dLGN to V1. V1, primary visual cortex; V2L, lateral secondary visual cortex; A1, primary auditory cortex; dLGN, dorsal lateral geniculate nucleus; LP, lateral posterior nucleus; MG, medial geniculate nucleus; SC, superior colliculus; IC, inferior colliculus; ICb, inferior colliculus brachium; CN, cochlear nucleus.

Figure 3

Ectopic retinal projections to the medial geniculate nucleus (MG) in the SC + ICb lesioned (or rewired) hamster. (a) Retinal projections in the MG labelled by intraocular injection of the cholera toxin β fragment and (b) co-tagged with wheat germ agglutinin-horse radish peroxidise (WGA-HRP). (c) Gold chloride myelin staining (left panel) and transneuronal labelling, with WGA-HRP (right panel), of new visual thalamo-cortical afferences reaching namely cortical layer IV in the primary auditory cortex (A1) (white arrow head). A1, primary auditory cortex; AuD, dorsal secondary auditory cortex; AuV, ventral secondary auditory cortex; TeA, temporal association cortex; PRh, perirhinal cortex; dLGN, dorsal lateral geniculate nucleus; vLGN, ventral geniculate nucleus; LP, lateral posterior nucleus; MG, medial geniculate nucleus; ot, optic track; IGL, intergeniculate leaflet.

Figure 4

Visual properties of single neurons in auditory and somatosensory cortices of rewired hamsters. These cells that responded to visual stimuli showed orientation selectivity, motion and direction sensitivity with receptive field properties similar with those obtained from neurons in the visual cortex of normal hamsters. (a) Examples of visual responsive neurons in the somatosensory cortex of hamsters with new retinal projections in the somatosensory ventrobasal nucleus (VB) of the thalamus adapted from Metin and Frost [83]. (b) Receptive field properties of visual neurons found in the auditory cortex of hamsters with ectopic retinal terminals in the auditory medial geniculate nucleus (MG). Orientation (left panel) and direction (right panel) selectivity adapted from Frost and collaborators [103]. V, vertical orientation; Ob, oblique orientation; Or, orientation selective; H, horizontal orientation; D, direction selective; Uni-D, unidirectional; Bi-D, bidirectional; NS, non-selective neuron.

Figure 5

Visually guided behavior in SC + ICb lesioned (or rewired) hamsters. (a) Example of the experimental setup with visual stimuli and Y maze. (b) Histograms showing trials to criterion on the visual discrimination tasks in normal hamsters before and after ablation of visual (VC) and auditory (AC) cortices. (c) Behavior of rewired hamsters before and after AC lesions. At the behavioral level, rewired hamsters can learn visual discrimination tasks as well as normal ones and a lesion of the auditory cortex abolishes this function. In fact, SC + ICb lesioned hamsters with auditory cortex lesions exhibit cortical blindness (*) similar to normal hamsters with visual cortex lesions. These results provide strong evidence for sensory substitution where a given sensory modality acquires the functional properties of a missing one. Adapted from Frost et al. [103] and Ptito et al. [95].

Figure 6

Laminar distribution of PV and CB expressing interneurons in the visual and auditory cortices of normal, enucleated and SC lesioned at birth hamsters. (a) Immunostaining patterns of the two CBP-IR neuronal subpopulations in V1 of normal and enucleated hamster. Left panels: cresyl violet staining with laminar boundaries; middle panels: photomicrographs of the distribution of PV and CB immunoreactivities; right panels: distribution of each CBP-IR neurons (black dots) plotted from three superimposed sampled sections. Black arrows indicate layer IV and V changes for PV-IR and CB-IR neurons between experimental groups. Pial surface of the cortices are at the top. Scale bars 100 μm. (b) Changes in the distributions of PV and CB neurons in layer IV and V of V1 compared to A1 in normal versus enucleated hamsters. (c) Alterations in the distribution of PV and CB interneurons in V1 and V2L of SC lesioned versus normal hamsters. Histograms illustrate the mean density number of neurons per mm³ of cortical layer and error bars represent SEM. Significant differences are represented by stars *P < 0.05, **P < 0.01 and ***P < 0.001. Adapted from Desgent et al. [29, 30].