Orienting behaviours and attentional processes in the mouse and macaque : neuroanatomy, electrophysiology and optogenetics

PhD ThesisThe neuronal basis of orienting and attentional behaviours has been widely researched in higher animals such as non-human primates (NHPs). However the organisation of these behaviours and processes in rodent models has been less well characterised. This thesis is motivated to delineate the key neuroanatomical pathways and neuronal mechanisms that account for orienting behaviours in the mouse model and compare them, in part, to those seen in the macaque. A better understanding of the processes and networks involved with attention and orienting is necessary in order to relate findings in the mouse model to those seen in humans and NHPs. Further to this, the availability of highly targeted manipulations in the mouse, such as optogenetics, requires a more detailed picture of the neurophysiology underpinning those behaviours to effectively interpret findings and design experiments to exploit these techniques and animal models for maximum benefit. In this thesis, study one focuses on the neuroanatomical pathways that terminate in subregions of the midbrain superior colliculus (SC) in the mouse (mus musculus) using iontophoretic injection of the retrograde tracer fluorogold. This region has been implicated in various forms of orienting behaviours in both macaques and mice (Albano et al., 1982, Dean et al., 1988b, Felsen and Mainen, 2008). Furthermore study one examines the prefrontal connectivity that links to the SC subsections and which may govern approach and avoidance behaviours (motor cortex area 2 (M2) and cingulate area (Cg)) in the mouse via pressure injection of the anterograde tracer biotinylated dextran amine into these regions. It was found that the medial and lateral SC receive differential prefrontal input from the Cg and M2 respectively. And that these areas project to brain networks related to avoidance or approach. This section furthers our understanding of the partially segregated networks which exist in the prefrontal cortex and midbrain of the mouse, which are important in mediation of different orienting behaviours Study two focuses on the effects of one type of orienting, namely bottom-up attention (BU) in visual areas. This exogenous (automatic) form of visual attention has been studied extensively in human psychophysics (Posner, 1980, Nakayama and Mackeben, 1989) and the areas involved in the human brain have been delineated using brain imaging (Corbetta and Shulman, 2002, Liu et al., 2005). To understand the neurophysiology involved, some electrophysiological invasive studies have been performed in the macaque monkeys, II ( Luck et al., 1997, Buschman and Miller, 2007), but our understanding of the mechanisms involved is relatively sparse when compared to top-down (endogenous) attentional processing. To understand the similarities in this mechanism between macaques and mice it is therefore important to study both model systems using similar approaches. The research of this chapter aims to make direct comparisons between these two model species via electrophysiological recordings in a bottom-up attentional paradigm. It was found that in the macaque BU cues increased responses to visual stimuli in both V1 and V4, but no obvious pattern was seen in the mouse V1 and SC. This study goes some way in describing the similarities and differences in neural responses in visual areas of different species which are utilised for attention based paradigms Finally study three focuses on linking the previous two studies. In study two we investigated bottom-up attentional processes, which are thought to involve early, fast visuomotor pathways. Whereas in study one we found that SC and V1, areas known for their involvement in and ability to coordinate rapid visuomotor responses, respectively, also receive clear and structured input from higher-level prefrontal areas. Therefore we hypothesized that stimulating these prefrontal areas could modulate bottom-up attention. This is achieved by using optogenetic stimulation of prefrontal control regions, such as Cg, identified in this research whilst preforming electrophysiological recordings in a bottom-up attentional paradigm. In V1 is was found that optogenetic stimulation had no effect on neuronal activation. However in SC optogenetic activation increased the sustained stimulus response, regardless of cuing condition. Taken together, this research further investigates some brain regions involved in orienting and attention in both mice and macaques and partially bridges the gap in understanding between these two animal models