Cholinergic Deafferentation of the Neocortex Using 192 IgG-Saporin Impairs Feature Binding In Rats

Abstract

The binding problem refers to the fundamental challenge of the CNS to integrate sensory information registered by distinct brain regions to form a unified neural representation of a stimulus. Although the human cognitive literature has established that attentional processes in frontoparietal cortices support feature binding, the neurochemical and specific downstream neuroanatomical contributions to feature binding remain unknown. Using systemic pharmacology in rats, it has been shown that the neuromodulator acetylcholine is essential for feature binding at encoding, but the neural source of such critical cholinergic neurotransmission has yet to be identified. Cholinergic efferents from the nucleus basalis magnocellularis (NBM) of the basal forebrain provide the majority of the cholinergic input to the neocortex. Accordingly, it was hypothesized that the NBM is the neural source that provides the critical neuromodulatory support for feature binding. To test this hypothesis, rats received bilateral 192 IgG-saporin lesions of the NBM, and their feature binding performance was tested using a forced-choice digging paradigm. Relative to sham-lesioned rats, NBM-lesioned rats were significantly impaired at acquiring a crossmodal feature conjunction (FC) stimulus set that required feature binding, whereas their ability to retrieve an FC stimulus set and to acquire two crossmodal feature singleton stimulus sets, one of greater difficulty than the other but neither requiring feature binding, remained intact. These behavioral findings, along with histological analyses demonstrating positive relationships between feature-binding acquisition and markers of cholinergic activity in frontoparietal regions, reveal the importance of neocortical cholinergic input from the NBM to feature binding at encoding.

Cortical cholinergic signaling controls the detection of cues

“…Cortical cholinergic activity is critically involved in sensory perception and attention (9,13,23,24). Here we demonstrate that ACh signaling is an essential mechanism mediating the utilization of environmental stimuli to guide behavior.…”

Early Visuospatial Deficits Predict the Occurrence of Visual Hallucinations in Autopsy-Confirmed Dementia With Lewy Bodies

“…Antagonizing the cholinergic muscarinic system resulted in disturbed initial feature binding in rats. (23–25) Visuospatial processing could be degraded in patients with DLB (and more so than in AD) by cholinergic deafferentation of visual association areas if such reductions in input result in the inability to either pull the salient features from the visual scene or to successfully reintegrate those features.…”

Modes and Models of Forebrain Cholinergic Neuromodulation of Cognition

“…Cortical cholinergic deafferentation did not affect the animals’ performance in blocks of unimodal trials in which all cues were either visual or auditory. In contrast, under the condition of modality uncertainty, the lesion caused a profound speed-accuracy trade-off, with correct responses requiring 700 ms longer in bimodal than in unimodal blocks of trials (for additional evidence illustrating disruption of basic attentional abilities by selective cholinergic lesions see, for example, Newman and McGaughy, 2008; Botly and De Rosa, 2009). The robustness and the selectivity of the cognitive impairments produced by such lesions is further supported, albeit indirectly, by a substantial number of experiments which concluded that removal of forebrain cholinergic neurons does not have strong effects on the performance of animals in tasks that do not explicitly tax attentional processes (Vuckovich et al , 2004; Frick et al , 2004).…”