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The Journal of Neuroscience, April 1, 2009, 29(13):4120-4130; doi:10.1523/JNEUROSCI.0654-09.2009

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Behavioral/Systems/Cognitive
Cholinergic Deafferentation of the Neocortex Using 192 IgG-Saporin Impairs Feature Binding In Rats

Leigh C. P. Botly¹ and Eve De Rosa^1,2

¹Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3, and ²Rotman Research Institute, Toronto, Ontario, Canada M6A 2E1

Correspondence should be addressed to either Leigh C. P. Botly or Eve De Rosa, Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario, Canada M5S 3G3. Email: leigh{at}psych.utoronto.ca or Email: derosa{at}psych.utoronto.ca

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.

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Received Feb. 8, 2009; accepted Feb. 24, 2009.

Correspondence should be addressed to either Leigh C. P. Botly or Eve De Rosa, Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario, Canada M5S 3G3. Email: leigh{at}psych.utoronto.ca or Email: derosa{at}psych.utoronto.ca

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