A prominent terminal field (red) stemming from the PV1-nucleus of the hypothalamus is located ventrolateral to the aqueduct at the level of the oculomotor nucleus (green). This terminal field forms a longitudinally-oriented cylinder, which spans approximately 450 ?m in length.

Celio Group

Neurosciences

The functions of the hypothalamus are so basic, that its anatomical plan and the organizational pattern have been conserved to a great extent throughout mammalian phylogeny.

The hypothalamus per se has been long suspected of triggering positive emotions, owing to the circumstance that hamartomas and vascular affections in its tuberal portion provoke bursts of laughter.
A prominent terminal field (red) stemming from the PV1-nucleus of the hypothalamus is located ventrolateral to the aqueduct at the level of the oculomotor nucleus (green). This terminal field forms a longitudinally-oriented cylinder, which spans approximately 450 ?m in length.
Electrophysiological studies in various species have indeed confirmed that hypothalamus -as part of the limbic system- contributes to laughter. However, only the rudiments of the neural circuit underlying the expression of positive emotions are known. The medial frontal cortex, the lateral hypothalamus and the periaqueductal grey matter (PAG) are involved; so, too, are centers in the brain stem subserving the mimic, respiratory and laryngeal muscles. The individual components of the circuit, viz., the implicated populations of neurons, have not been defined either anatomically or molecularly.

With our recent discovery of the PV1-nucleus in the medial forebrain bundle of rodents (Meszar et al., 2012) -which we deem to be the counterpart of the lateral tuberal nucleus (LTN) in primates- (Gerig and Celio, 2007; Girard et al., 2011) this situation is now likely to change. Using molecularly-defined nuclei as a centerpiece, the projections and the inputs can be studied with precision. And using an optogenetic approach, it will be possible to selectively manipulate the circuitry with high spatial and temporal precision. By combining this optogenetic approach with electrophysiological recordings in alert, behaviourally unrestrained animals, the functional contribution of subcortical cell populations to neural processing in the “happiness” circuit can be studied. These data can then be used as a basis for fMRI-studies in humans using the laughing paradigm to provoke joyful emotions (Wattendorf et al., 2012).

Of the five basic emotions – fear, anger, disgust, sorrow and happiness – only the latter is positive. The lateral hypothalamus may represent the centerpiece for “happiness” as the amygdala is for fear, and the insula for disgust.

Experiments are performed with a wide panel of different techniques: morphology (e.g. in situ hybridization), tract tracing with viral constructs, biochemistry, molecular-biology (e.g. gene-microarrays), magnetic resonance imaging (in humans), and behavioral studies.

Funding

  • Intramural budget (University of Fribourg)
  • Private foundations (Novartis foundation)
  • Swiss National Science Foundation