**7. Nicotinic-muscarinic interaction in memory and cognition**

Cholinergic system is implicated in memory and cognition functions. ACh is diffusely released throughout the cortex during periods of high attentional demand which could act on nAChRs and mAChRs, both of which are critically important

#### *Central Nicotinic and Muscarinic Receptors in Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.112447*

in cognitive processes such as learning, memory, attention, and other higher brain functions. Manipulation of these receptors exert distinguishable effects on different cognitive functions. For instance, working memory is required for remembering information that varies unpredictably in time and/or in content. It refers to the cognitive system that holds information temporarily and is important for reasoning and decision-making. In contrast, reference memory is a long-term memory that deals with the recall of the content and place of an event.

Both mAChRs and nAChRs modulate not only working and reference memory, but other indices of cognitive functions such as attention and learning. For example, muscarinic M1 receptors in prefrontal cortex [26, 27], and nicotinic receptors, particularly α7 and α4β2 receptors, modulate firing of dorsolateral prefrontal cortex excitatory networks that underlie working memory function [28, 29]. Moreover, muscarinic M1 receptors, may also interact with glutamatergic NMDA receptors in regulation of working memory [30].

Several pharmacological studies have attempted to disentangle the role of nAChRs and mAChRs in different cognitive domains. Blocking mAChRs by scopolamine causes impairment of different aspects of memory processing such as acquisition of new information, consolidation of memory, sustained attention, reaction time, as well as visual discrimination [31, 32]. Antagonism of nAChRs, on the other hand, affects declarative memory (immediate and delayed word recall and delayed recognition), attention and psychomotor function (reaction time), suggesting that attention and psychomotor (reaction time) may be mediated by both mAChRs and nAChRs. This contention is further supported by the findings that blockade of both mAChRs and nAChRs impair working memory (spatial and non-spatial), short-term memory, declarative memory, sustained visual attention, and psychomotor function far more than each antagonist alone [33]. Similar observations were also seen in object and spatial n-back working memory performance where simultaneous antagonism of mAChRs and nAChRs produced greater effect than each antagonist alone [34].

In another cognitive domain, inspection time (IT), a measure of early visual information processing speed, it was determined that the efficiency of visuospatial attention is sensitive to manipulation by both nAChRs and mAChRs. Simultaneous antagonism of both mAChRs and nAChRs induced larger impairments in early information processing (in an inspection time task) than antagonism of either receptor alone [31]. Curiously, impairments in early information processing, a hallmark feature of diverse neuropsychiatric disorders including schizophrenia and AD, may contribute to impairments in other cognitive domains including attention and memory. It is of relevance to note that age-related alterations in mAChR and nAChR interactions also occur [35]. Hence, several lines of evidence implicate a dysfunction of the cholinergic system in cognitive dysfunctions including in AD. This topic is further discussed below, mainly in relationship to AD and PD.
