**3.3 Novelty-induced realese of acetylcholine**

Historically, ACh has been implicated in cognitive functions such as learning and short-term memory, as well as dysfunction in central cholinergic transmission was linked to learning and memory impairment present in patients with Alzheimer's disease and other forms of dementia [Bartus et al., 1982; Bartus et al., 1985; Coyle et al., 1983; Collerton, 1986; Davies et al., 1987; Blokland, 1995; Muir, 1997; Francis et al., 1999].

However, brain areas, which are supposingly most important for attentional processing in both animals and humans, appear to be the prefrontal, parietal and somatosensory (especially visual) regions, where ACh plays an essential role in the control of attentional orienting and stimulus discrimination. In addition, cholinergic signaling in the septohippocampal system is suggested to be involved in memory processes.

*Trait d'union* between cortical areas and hippocampus in attention and cognition is the *basal forebrain cholinergic system* [Mesulam et al., 1983]. To this purpose a lot of studies have been carried out in animals and humans, investigating the role of ACh in attention and cognition. Animal behavioral studies have been performed both in intact and in compromised brain cholinergic transmission, such as in animals subjected to specific cholinergic lesions by toxins or pharmacologically induced amnesia using muscarinic or nicotinic antagonists [Dunnett et al., 1990]. Human studies, which can give some indication on the link between central cholinergic signaling and cognition, are obviously confined to less invasive imaging methods such as fMRI.

Therefore, a large body of researches has contributed to elucidate better the role of ACh in cognitive functions. In contrast to a general role in learning and memory, recent insights have refined the function of cortical ACh more specifically in attentional effort and orienting, and detection of behavioral significant stimuli [Sarter and Bruno, 1997].

Since both ACh release and theta oscillations are affected by a range of factors, testing animals in more settings may be needed to elucidate the nature of novelty effects on hippocampal theta oscillations and phasic ACh release.

8 Advances in Object Recognition Systems

hippocampal theta frequency dropped (by about 0.6 Hz) when the rats were tested in a novel environment [Jeewajee et al., 2008]. This change in theta frequency might function as a novelty signal because hippocampal theta frequency is the same in the whole hippocampus [Buzsaki, 2002], and they suggested that the reduction in theta frequency would have implications for memory encoding. The authors speculate that novelty leads a lowfrequency theta depending on acetylcholine release. In fact, it is well known that new experience and novel environment induces in brain increase in cholinergic input to the hippocampus and increase in ACh release which affects hippocampal theta activity [Givens and Olton, 1994, 1995; Podol'skii et al., 2001]. On the other hand, other authors did not find any change in peak theta frequency when animals were stimulated by a novel environment; they instead reported a change in theta power that differentiated active from passive behavior, with novelty increasing power at both levels of activity [Sambeth et al., 2009].

Nevertheless, taken together both findings suggest that theta oscillations in hippocampus are affected by novelty, and that this probably gives reasons for hippocampal learning.

Historically, ACh has been implicated in cognitive functions such as learning and short-term memory, as well as dysfunction in central cholinergic transmission was linked to learning and memory impairment present in patients with Alzheimer's disease and other forms of dementia [Bartus et al., 1982; Bartus et al., 1985; Coyle et al., 1983; Collerton, 1986; Davies et

However, brain areas, which are supposingly most important for attentional processing in both animals and humans, appear to be the prefrontal, parietal and somatosensory (especially visual) regions, where ACh plays an essential role in the control of attentional orienting and stimulus discrimination. In addition, cholinergic signaling in the

*Trait d'union* between cortical areas and hippocampus in attention and cognition is the *basal forebrain cholinergic system* [Mesulam et al., 1983]. To this purpose a lot of studies have been carried out in animals and humans, investigating the role of ACh in attention and cognition. Animal behavioral studies have been performed both in intact and in compromised brain cholinergic transmission, such as in animals subjected to specific cholinergic lesions by toxins or pharmacologically induced amnesia using muscarinic or nicotinic antagonists [Dunnett et al., 1990]. Human studies, which can give some indication on the link between central cholinergic signaling and cognition, are obviously confined to less invasive imaging

Therefore, a large body of researches has contributed to elucidate better the role of ACh in cognitive functions. In contrast to a general role in learning and memory, recent insights have refined the function of cortical ACh more specifically in attentional effort and

Since both ACh release and theta oscillations are affected by a range of factors, testing animals in more settings may be needed to elucidate the nature of novelty effects on

orienting, and detection of behavioral significant stimuli [Sarter and Bruno, 1997].

septohippocampal system is suggested to be involved in memory processes.

**3.3 Novelty-induced realese of acetylcholine** 

methods such as fMRI.

al., 1987; Blokland, 1995; Muir, 1997; Francis et al., 1999].

hippocampal theta oscillations and phasic ACh release.

In conclusion, some indications can be given. Prefrontal cortex regions are involved in shortterm memory and object discrimination. Cholinergic signaling, coming from basal forebrain to frontal cortex, septum and hippocampus, are implicated in short-term memory; in addition, the hippocampus could be important for discrimination processes in cognition.
