Nicotinic alteration of functional thalamocortical topography

Abstract

The thalamocortical pathways form highly topographic connections from the primary sensory thalamic nuclei to the primary cortical areas. The synaptic properties of these thalamocortical connections are modifiable by activation from various neuromodulators, such as acetylcholine. Cholinergic activation can alter functional properties in both the developing and the mature nervous system. Moreover, environmental factors, such as nicotine, can activate these receptors, although the circuit-level alterations resulting from such nicotinic activation of sensory neural circuits remain largely unexplored. Therefore, we examined alterations to the functional topography of thalamocortical circuits in the developing sensory pathways of the mouse. Photostimulation by uncaging of glutamate was used to map these functional thalamocortical alterations in response to nicotinic receptor activation. As a result, we found that activation of forebrain nicotinic acetylcholine receptors results in an expansion and enhancement of functional thalamocortical topographies as assessed in brain slice preparations using laser-scanning photostimulation by uncaging of glutamate. These physiological changes were correlated with the neuroanatomical expression of nicotinic acetylcholine receptor subtypes (α7 and β2). These circuit-level alterations may provide a neural substrate underlying the plastic development and reshaping of thalamocortical circuitry in response to nicotinic receptor activation.

Figure 1

Cholinergic alterations to functional topography in the auditory thalamocortical slice. A. Whole-cell patch clamp recorded responses from a layer 4 neuron in the primary auditory cortex (A1) following laser-scanning photostimulation (LSPS) of the auditory thalamus, medial geniculate body (MGB). Panels A and D depict photomicrographs of the MGB with recorded traces from the layer 4 neuron superimposed on the spatial location in the thalamus that elicited the response following LSPS. Recordings in voltage clamp mode. Downward deflections in the traces indicate excitatory postsynaptic current (EPSCs) responses. B. The peak amplitude of the EPSCs in A are plotted, with hot colors indicating bigger amplitudes, as indicated by the scale bar. C. The onset response latencies of the EPSCs in A are plotted, with cooler colors indicating longer latencies, as indicated by the scale bar. D. Bath application of nicotine results in alterations to evoked responses. The same thalamic region is photostimulated again following application of nicotine to the bath and changes to the peak amplitudes and latencies were observed. Compare traces at similar grid locations with those in panel A. E. Plot of peak responses in D, in the same manner as described for panel B. F. Plot of onset latencies in D, in the same manner as described for panel C. Figure abbreviations: Hip, hippocampus; L, lateral; MGB, medial geniculate body; R, rostral.

Figure 2

Cortical and thalamic expression of nicotinic acetylcholine receptor (nAChR) subtype β2. A. Laminar expression of nAChR β2 (red puncta) in the primary auditory cortex (A1), relative to VGAT-positive inhibitory neurons (green cells). Photomontage of A1 labeling following immunohistochemistry for nAChR β2 (red puncta) and DAPI staining (blue cells) in a VGAT-Venus transgenic mouse that expresses Venus fluorescent protein in inhibitory neurons (green cells). B. Terminals positive for nAChR β2 (red puncta) terminate on cell bodies that are primarily non-inhibitory (blue cells), while inhibitory neurons (green cells) have completely no puncta juxtaposed. Higher magnification view of upper cortical layers in panel A. C. Thalamic expression of nAChR β2 is completely absent. Figure abbreviations: C, caudal; Hip, hippocampus; L, lateral; MGB medial geniculate body.