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The Effects of Cholinergic and Noradrenergic Deafferentation of the Cortex on Memory and Attention

Jill McGaughy, Michael Hasselmo and Howard Eichenbaum
Centre for Memory and Brain, Boston University, USA

Normal and pathological aging is correlated with degeneration in both the cholinergic and noradrenergic systems. The importance of the cholinergic system in sustained and divided attention has been well supported in recent years. However, less is known about the role of ACh in other types of cognition or the role of NE in attention. In humans, the medial temporal lobes are specifically activated during working memory for novel, but not familiar stimuli (Stern et al. 2001) and cholinergic deafferentation of the rhinal cortex in non-human primates has been shown to impair memory for trial-unique (novel) stimuli (Turchi et al. SFN abstracts v. 28). Currently, the effects of cholinergic deafferentation of the entorhinal cortex (EC) were tested in an odor, delayed non-match to sample task (DNMS) using rats. Rats were impaired in recognition memory for novel, but not familiar odors.  The impairment cannot be explained by an increased sensitivity to task difficulty as a result of the lesion. These data support the hypothesis that cholinergic afferents to the EC activate cellular mechanisms of sustained spiking activity necessary for maintenance of novel, but not familiar stimuli in a working memory task (Fransen et al. 2002). In a second study, the effects of noradrenergic or cholinergic deafferentation of the infralimbic/prelimbic cortex of rats in an attentional set-shifting task (Birrell and Brown 2000) were examined. The noradrenergic lesions caused impairments in the broadening of attentional scope necessary to attend to a newly relevant stimuli dimension (extra-dimensional shift) but did not affect other aspects of the task. Lesions of the cholinergic afferents did not alter attentional set-shifting but impaired the ability to inhibit responding to novel, but irrelevant stimuli. These data do not support a simple dissociation of the effects of ACh and NE on cognition along temporal or spatial dimensions and highlight the need to consider the functions of these systems based on their termination rather than origin.

Birrell J, Brown V (2000)
Medial frontal cortex mediates perceptual attentional set shifting in the rat. The Journal of Neuroscience 20:4320-4324

Fransen, E, Alonso, AA and Hasselmo, ME (2002)
Simulations of the role of the muscarinic-activated calcium-sensitive non-specific cation current I(NCM) in entorhinal neuronal activity during delayed matching tasks. J.Neurosci. 22(3):1081-1097

Stern CE, Sherman SJ, Kirchhoff BA, Hasselmo ME (2001)
Medial temporal and prefrontal contributions to working memory tasks whith novel and familiar stimuli. Hippocampus 11:337-346.

Turchi, JN,  Saunders, RC, Mishkin, M (2002)
Effects of cholinergic deafferentation of rhinal cortex on visual recognition in monkeys. Program no. 82.5. 2002 Abstract Viewer/itinerary planner. Washington, DC: Society for Neuroscience, 2002. Online.