How do medial amygdala (MeA) excitatory neurons control behavioural responses to olfactory stimuli?

The medial amygdala (MeA) is an important brain region thought to be responsible for controlling a variety of social and emotional behaviours. It receives and sends projections to many other brain areas relevant to these functions. Interestingly, the MeA is highly heterogenous comprising distinct populations of glutamatergic (Glut) and GABAergic projection neurons. The functional significance of these projections in terms of their function in controlling these complex functions is only just coming to light. Importantly, the MeA receives olfactory information and is thought to transfer this information to forebrain centres involved in defense and reproduction. Interestingly, recent evidence suggests that the MeA sends direct projections to the paraventricular nucleus of hypothalamus (PVN) but the functional importance of this pathway in responding to olfactory stimuli is unclear. In this thesis, we firstly examined whether optogenetic activation of the MeAGlut àPVN pathway promotes behavioural reactivity relevant to stress or threat reactivity. Acute stimulation of the MeAGlut àPVN increased locomotor activity possibly reflecting selection of acute escape or flight behaviour. Next, we tested the effect of inhibiting this pathway using a retrograde inhibitory halorhodopsin and examined the impact of this manipulation and animals’ interaction with olfactory stimuli. These data suggested that inhibition of the MeAGlut àPVN pathway might increase approach behaviour. To provide further information relevant to this question, we examined the activity of MeAGlut neurons in response to olfactory stimuli using the genetically encoded Ca+2-indicator GCaMP6f. These data demonstrated that the activity of MeAGlut neurons increased on approach to novel and threatening olfactory stimuli. Interestingly, a trend towards increased MeAGlut activity on withdrawal from dirty rat bedding was observed. A simplistic interpretation of these findings is that activity of MeAGlut neurons is important for both approach and avoidance and that the strength of this response dictates the behavioural outcome.