Neural connectivity between the hypothalamic supramammillary nucleus and appetite‐ and motivation‐related regions of the rat brain

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.

Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1

“…Serotonin depletion of the SuM leads to deficiencies in spatial learning in the Morris water maze, and results in altered hippocampal theta activity ( Gutiérrez-Guzmán et al, 2012 ; Hernández-Pérez et al, 2015 ). Salient rewarding experiences also activate the SuM, as evidenced by cFos expression in monoaminergic SuM neurons by consumption of rewarding food ( Plaisier et al, 2020 ). Furthermore, the rewarding aspects of social aggression have been shown to involve an excitatory circuit between the hypothalamic ventral premammillary nucleus and the SuM ( Stagkourakis et al, 2018 ).…”

The rostral intralaminar nuclear complex of the thalamus supports striatally-mediated action reinforcement

“…Although less studied, the SUM is well connected with mesolimbic circuitry and linked to regulation of feeding behavior (Plaisier et al, 2020). Together, these afferents may impart value and motivation for rILNDS guided action selection.…”

“…The OFC encodes outcome value (Gremel & Costa, 2013; Malvaez et al, 2019; Stolyarova & Izquierdo, 2017; Zhou et al, 2019), whereas the ACC encodes decision predictions, surprise signals, and prediction errors, in addition to mediating cognitive control (Hayden et al, 2011; Shenhav et al, 2013; Totah et al, 2009; Wallis & Kennerley, 2011). Although less studied, the SUM is well connected with mesolimbic circuitry and linked to regulation of feeding behavior (Plaisier et al, 2020). Together, these afferents may impart value and motivation for rILN→DS guided action selection.…”

Assessing the treatment of cannabidiolic acid methyl ester: a stable synthetic analogue of cannabidiolic acid on c-Fos and NeuN expression in the hypothalamus of rats

“…In detail, slides from control and HU-580 groups (0.1 or 100 μg/kg; i.p.) were prepared for c -Fos and NeuN immunohistochemical analysis using standardized procedures as previously described (Ni et al 2020 ; Plaisier et al 2020 ). Serial coronal cryostat sections of the DMD, DMC, and DMV were processed for c -Fos and NeuN immunoreactivity, imaged, and quantified as described previously (de-la-Cruz et al 2018 ).…”