Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 May 6;29(18):5992-6000.
doi: 10.1523/JNEUROSCI.0230-09.2009.

The Basal Forebrain Cholinergic System Is Required Specifically for Behaviorally Mediated Cortical Map Plasticity

Affiliations
Free PMC article

The Basal Forebrain Cholinergic System Is Required Specifically for Behaviorally Mediated Cortical Map Plasticity

Dhakshin Ramanathan et al. J Neurosci. .
Free PMC article

Abstract

The basal forebrain cholinergic system has been implicated in the reorganization of adult cortical sensory and motor representations under many, but not all, experimental conditions. It is still not fully understood which types of plasticity require the cholinergic system and which do not. In this study, we examine the hypothesis that the basal forebrain cholinergic system is required for eliciting plasticity associated with complex cognitive processing (e.g., behavioral experiences that drive cortical reorganization) but is not required for plasticity mediated under behaviorally independent conditions. We used established experimental manipulations to elicit two distinct forms of plasticity within the motor cortex: facial nerve transections evoke reorganization of cortical motor representations independent of behavioral experience, and skilled forelimb training induces behaviorally dependent expansion of forelimb motor representations. In animals that underwent skilled forelimb training in conjunction with a facial nerve lesion, cholinergic mechanisms were required for mediating the behaviorally dependent plasticity associated with the skilled motor training but were not necessary for mediating plasticity associated with the facial nerve transection. These results dissociate the contribution of cholinergic mechanisms to distinct forms of cortical plasticity and support the hypothesis that the forebrain cholinergic system is selectively required for modulating complex forms of cortical plasticity driven by behavioral experience.

Figures

Figure 1.
Figure 1.
Experimental paradigm. Three experiments were conducted in this study. Experiment 1, An initial experiment (10 rats) determined whether cholinergic mechanisms were required for mediating plasticity of cortical motor representations acutely following facial nerve transections (FNL), whereby plasticity is induced rapidly (within minutes to hours) and occurs independent of behavioral activity. Experiment 2, A second experiment (23 rats) examined whether the long-term maintenance of cortical plasticity following a facial nerve transection is dependent on cholinergic mechanisms. Experiment 3, A final experiment (32 rats) examined the effects of selective cholinergic depletion on cortical plasticity mediated concurrently by nonbehavioral (facial nerve transection) and behavioral (skilled motor training) paradigms within the same animal. See text for detailed methods use in each experiment.
Figure 2.
Figure 2.
Injection of 192 IgG-saporin into the nucleus basalis selectively eliminates cholinergic innervation to the sensorimotor cortex. A, Normal acetylcholinesterase cholinergic fiber histochemistry within layer 2/3 of motor cortex. B, Following injections of the cholinergic-specific immunotoxin 192-IgG-saporin into the nucleus basalis and substantia inominata, there is almost a complete loss of afferent cholinergic innervation to the cortex. Within the nucleus basalis and substantia inominata, 192-IgG SAP injections eliminate nearly all ChAT-positive cholinergic neurons (D) when compared with ACSF-injected controls (C). Immunohistochemical staining for parvalbumin (parv), a marker for basal forebrain GABAergic neurons, indicated nearly identical patterns in animals receiving either ACSF (E) or SAP (F), thus confirming the selectivity of the immunotoxin for the cholinergic component of the basal forebrain.
Figure 3.
Figure 3.
Plasticity following an acute facial motor nerve transection does not require the basal forebrain cholinergic system. A modified ICMS approach was used to characterize cortical plasticity acutely following a facial nerve lesion. A, A typical map from an intact animal, derived using standard ICMS techniques, wherein movements evoked with the lowest stimulation threshold are recorded. B, High amplitude stimulation within the vibrissa region in the same animal, using currents up to 200μA, reveals additional movements of the neck or forelimb, potentially revealing inputs that may be “unmasked” by a subsequent facial nerve transection (see Materials and Methods for details). At some vibrissa sites, high amplitude stimulation elicited only vibrissa movements, whereas at other vibrissa sites (crosshatch area), additional neck and forelimb movements were evoked at higher stimulus intensities. Calculation of pretransection representational areas was made based on high amplitude stimulation to control for the potential confound of unmasking in measurements of map expansion after facial nerve lesions. C, Following a facial nerve transection, the neck representation expands, but the forelimb representation does not. D, Quantification of changes in motor maps across all groups reveals that no significant plasticity of caudal forelimb representations occurs in either SAP-injected or ACSF-injected groups following facial nerve transection (p = 0.8; unpaired t test comparing SAP and ACSF groups). E, In contrast, facial nerve transection results in significant plasticity of neck representation in both SAP- and ACSF-injected animals (overall ANOVA, p < 0.001; individual paired t tests p < 0.01 for both ACSF and SAP groups). The extent of plasticity occurring in the neck representation does not differ between SAP-injected and ACSF-injected subjects (p > 0.2 unpaired t tests). Thus, the behaviorally independent plasticity that occurs immediately following a facial nerve transection is not cholinergic-dependent.
Figure 4.
Figure 4.
Long-term maintenance of plasticity following a facial motor nerve transection does not require basal forebrain cholinergic mechanisms. A, Significant plasticity of neck representations is chronically sustained 6 weeks after facial nerve transection (ANOVA p < 0.01; all groups differ from pretransection group on Tukey–Kramer post hoc, p < 0.01). Moreover, depleting cholinergic innervation to the cortex does not affect the expression or maintenance of facial nerve transection-induced plasticity: the extent of neck representation plasticity at long-term time points does not differ between SAP-injected and ACSF-injected subjects (p = 0.8, post hoc Tukey–Kramer). B, As was observed acutely following a facial nerve transection, plasticity of the caudal forelimb representations did not occur at long-term time points (ANOVA, p > 0.05).
Figure 5.
Figure 5.
Basal forebrain cholinergic ablation impairs acquisition of skilled forelimb reaching. Ablation of cortical cholinergic innervation results in a significant impairment in acquisition of skilled forelimb grasping (repeated measures ANOVA, p < 0.001; *significant differences in performance on individual days, p < 0.01). All subjects underwent facial nerve transactions before beginning skilled forelimb reach training.
Figure 6.
Figure 6.
Cholinergic ablation selectively abolishes plasticity associated with behavioral experience. A–D, Representative motor maps of different animals from each experimental group (intact animal, long-term postfacial nerve lesion, and animals with facial nerve lesions with training, with and without a lesion of the basal forebrain cholinergic system). These maps demonstrate that cholinergic ablation prevents experience-dependent plasticity (expansion) of the caudal forelimb representation associated with skilled motor training but does not affect plasticity of neck representations generated by a facial nerve transection. E, F, Quantification of map plasticity across all experimental subjects. E, Skilled motor training results in significant expansion of caudal forelimb representations compared with all other groups (ANOVA, p < 0.0001; Tukey–Kramer HSD post hoc tests, p < 0.05; comparing trained animals to all other groups), and this behaviorally mediated plasticity is blocked by selective ablation of cortical cholinergic innervation (p = 0.35 Tukey–Kramer HSD post hoc comparing animals with a facial nerve lesion alone to trained animals with SAP lesions and facial nerve lesions). F, In contrast, cholinergic ablation has no effect on behaviorally independent plasticity of neck representations induced by a facial nerve transection (ANOVA, p < 0.01; p < 0.05, Tukey–Kramer HSD post hoc comparing intact to all facial nerve transected subjects. No other significant differences were seen.).

Similar articles

See all similar articles

Cited by 37 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback