Behavioral Sequence Analysis Reveals a Novel Role for ß2* Nicotinic Receptors in Exploration

Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the central nervous system and modulate neuronal function in most mammalian brain structures. The contribution of defined nAChR subunits to a specific behavior is thus difficult to assess. Mice deleted for ß2-containing nAChRs (ß2−/−) have been shown to be hyperactive in an open-field paradigm, without determining the origin of this hyperactivity. We here develop a quantitative description of mouse behavior in the open field based upon first order Markov and variable length Markov chain analysis focusing on the time-organized sequence that behaviors are composed of. This description reveals that this hyperactivity is the consequence of the absence of specific inactive states or “stops”. These stops are associated with a scanning of the environment in wild-type mice (WT), and they affect the way that animals organize their sequence of behaviors when compared with stops without scanning. They characterize a specific “decision moment” that is reduced in ß2−/− mutant mice, suggesting an important role of ß2-nAChRs in the strategy used by animals to explore an environment and collect information in order to organize their behavior. This integrated analysis of the displacement of an animal in a simple environment offers new insights, specifically into the contribution of nAChRs to higher brain functions and more generally into the principles that organize sequences of behaviors in animals. Author Summary: Understanding mechanisms underlying complex behaviors and the abnormalities that accompany most neuropathologies is a current challenge in biomedical research. A number of approaches is primarily based on the identification of genes and their associated molecular pathways implicated in complex motor or cognitive pathologies. However, optimal use of the large body of genetic, molecular, electro-physiological, and imaging data is hampered by the practical and theoretical limitations of currently available behavioral analysis methods. Complex behaviors consist of a finite number of actions combined in a variety of spatial and temporal patterns. In this paper we develop a sequential analysis of mouse displacement in an open-field paradigm and demonstrate that a description based on a Markov model can be used to describe quantitatively patterns of behaviors and to detect changes in the way that animals organize their displacement, especially in mice lacking nicotinic acetylcholine receptor subunits. This paper would be of broad interest not only to those concerned with this particular mice model but also generally to those interested in modeling complex behavior traits in mice.