Abstract
The supramammillary nucleus (SuM) has an emerging role in appetite control. We have shown that the rat SuM is activated during hunger or food anticipation, or by ghrelin administration. In the present study, we characterised the connectivity between the SuM and key appetite‐ and motivation‐related nuclei in the rat. In adult wild‐type rats, or rats expressing Cre recombinase under the control of the tyrosine hydroxylase (TH) promoter (TH‐Cre rats), we used c‐Fos immunohistochemistry to visualise and correlate the activation of medial SuM (SuMM) with activation in the lateral hypothalamic area (LH), the dorsomedial hypothalamus (DMH) or the ventral tegmental area (VTA) after voluntary consumption of a high‐sugar, high‐fat food. To determine neuroanatomical connectivity, we used retrograde and anterograde tracing methods to specifically investigate the neuronal inputs and outputs of the SuMM. After consumption of the food there were positive correlations between c‐Fos expression in the SuMM and the LH, DMH and VTA (P = 0.0001, 0.01 and 0.004). Using Fluoro‐Ruby as a retrograde tracer, we demonstrate the existence of inputs from the LH, DMH, VTA and ventromedial hypothalamus (VMH) to the SuMM. The SuMM showed reciprocal inputs to the LH and DMH, and we identified a TH‐positive output from SuMM to DMH. We co‐labelled retrogradely‐labelled sections for TH in the VMH, or for TH, orexin and melanin‐concentrating hormone in the LH and DMH. However, we did not observe any colocalisation of immunoreactivity with any retrogradely‐labelled cells. Viral mapping in TH‐Cre rats confirms the existence of a reciprocal SuMM‐DMH connection and shows that TH‐positive cells project from the SuMM and VTA to the lateral septal area and cingulate cortex, respectively. These data provide evidence for the connectivity of the SuMM to brain regions involved in appetite control, and form the foundation for functional and behavioural studies aiming to further characterise the brain circuitry controlling eating behaviours.
Highlights
A picture is gradually emerging of the functional and anatomical connectivity between the neuroanatomically defined brain regions involved in appetite control
Recent findings provide evidence indicating that the supramammillary nucleus (SuM) may be involved in metabolic control
We previously showed that the activity of SuM neurones is sensitive to ghrelin administration or to physiological states where ghrelin levels are elevated, and that intra-SuM ghrelin administration promotes feeding.[1]
Summary
A picture is gradually emerging of the functional and anatomical connectivity between the neuroanatomically defined brain regions involved in appetite control. Understanding these circuits is currently one of the most challenging barriers to the development of treatment options for eating disorders and obesity. The lateral SuM (SuML) appears to play a role in the generation and maintenance of hippocampal theta rhythm, and the medial SuM (SuMM) contains tyrosine hydroxylase (TH)-positive neurones that project to areas involved in motivated behaviours such as the lateral septal nucleus and lateral hypothalamic area.[6,7] Classic tracing studies have deciphered the connectivity of the SuM with respect to its role in memory; the potential connectivity of the SuM with reward and appetite-associated regions has not yet been investigated systematically. We used retrograde and anterograde tracers, and Cre-dependent viral vector-assisted mapping to trace the afferent and efferent connections of SuMM neurones with these feeding behaviour-associated brain regions
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