Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression

<p>Abstract</p> <p>Background</p> <p>Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The neurobiological underpinnings of these conditioned responses are not well understood. Monitoring regional immediate early gene expression is a method used to assess alterations in neuronal metabolism resulting from upstream intracellular and extracellular signaling. Furthermore, assessing the expression of multiple immediate early genes offers a window onto the possible sequelae of exposure to food cues, since the function of each gene differs. We used immediate early gene and proenkephalin expression as a means of assessing food cue-elicited regional activation and alterations in functional connectivity within the forebrain.</p> <p>Results</p> <p>Contextual cues associated with palatable food elicited conditioned motor activation and corticosterone release in rats. This motivational state was associated with increased transcription of the activity-regulated genes <it>homer1a</it>, <it>arc</it>, <it>zif268</it>, <it>ngfi-b </it>and c-<it>fos </it>in corticolimbic, thalamic and hypothalamic areas and of proenkephalin within striatal regions. Furthermore, the functional connectivity elicited by food cues, as assessed by an inter-regional multigene-expression correlation method, differed substantially from that elicited by neutral cues. Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the shell towards the core. Exposure to the food-associated context also induced correlated gene expression between corticostriatal networks and the basolateral amygdala, an area critical for learning and responding to the incentive value of sensory stimuli. This increased corticostriatal-amygdalar functional connectivity was absent in the control group exposed to innocuous cues.</p> <p>Conclusion</p> <p>The results implicate correlated activity between the cortex and the striatum, especially the nucleus accumbens core and the basolateral amygdala, in the generation of a conditioned motivated state that may promote excessive food intake. The upregulation of a number of genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. As many of these genes play a role in plasticity, their upregulation within these circuits may also indicate the neuroanatomic and transcriptional correlates of extinction learning.</p

Circadiane slaap-waakritmestoornissen

Circadiane slaap-waakritmestoornissen zijn slaap-waakverstoringen met een afwijkend 24-uurspatroon in de slaap-waakafwisseling. In de psychiatrische praktijk komt de vertraagd slaap-waakritmestoornis (DSPD) veruit het vaakst voor. De prevalentieschatting van DSPD in de algemene bevolking varieert van 0,1 tot 3 %, oplopend bij jongeren tot 16 %. Klachten zijn problemen met op de gewenste tijd in slaap vallen en ’s morgens niet op tijd wakker kunnen worden, met slaperigheid en vermoeidheid overdag. Op de gewenste, late tijd wordt wel normaal geslapen. Naar schatting 40 % van de mensen met DSPD heeft ook een psychiatrische diagnose, zoals een stemmings-, angst- of middelengerelateerde stoornis. Therapie van vooral vertraagd slaap-waakritmestoornissen moet zich richten op een gedragsmatige slaapbehandeling in combinatie met weinig licht in de avond, lichttherapie in de ochtend en eventueel een lage dosis melatonine zo’n 5 uur voor het in slaap vallen