In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.

Using sensory information for the prediction of future events is essential for survival. Midbrain dopamine neurons are activated by environmental cues that predict rewards, but the cellular mechanisms that underlie this phenomenon remain elusive. We used in vivo voltammetry and in vitro patch-clamp electrophysiology to show that both dopamine release to reward predictive cues and enhanced synaptic strength onto dopamine neurons develop over the course of cue-reward learning. Increased synaptic strength was not observed after stable behavioral responding. Thus, enhanced synaptic strength onto dopamine neurons may act to facilitate the transformation of neutral environmental stimuli to salient reward-predictive cues. Dopamine (DA) neurons, originating in the ventral tegmental area (VTA) and substantia nigra and projecting to forebrain areas, are essential for the expression of goal-directed behaviors for both natural rewards and drugs of abuse (1-3). DA neurons are initially phasically activated by primary rewards such as food but shift their activation to reward-predictive stimuli after extended conditioning (4). Although DA signaling appears to be plastic, and can be modified by manipulating the contingency between conditioned stimuli and rewards (5), the cellular mechanisms that underlie this cue-reward learning remain unclear.Long-term potentiation (LTP) and long-term depression (LTD) are hypothesized cellular mechanisms for learning and memory storage (6). Glutamatergic synapses onto DA neurons can express LTP (7,8), LTD (9-11), and short-term plasticity (7). Furthermore, passive (12-14) or voluntary (15) exposure to cocaine can lead to long-lasting changes in synaptic function in DA neurons. Although excitatory synapses are highly plastic, it is unknown whether associative learning leads to synaptic alterations onto DA neurons.Both the firing of VTA neurons and the release of DA are time-locked to receipt of unpredicted rewards as well as to conditioned stimuli that predict reward delivery (16,17). However, the time course in which DA release develops to reward-predictive stimuli is poorly characterized. Thus, we used fast-scan cyclic voltammetry (FSCV) (figs. S1 and S2 and table S1) (18) to monitor rapid DA fluctuations in the nucleus accumbens (NAc) of rats during the acquisition of a cue-reward association in a Pavlovian conditioning task. Rats (n = 8) underwent single or

Striatal dopamine (DA) is thought to code for learned associations between cues and reinforcers and to mediate approach behavior toward a reward. Less is known about the contribution of DA to cognitive flexibility—the ability to adapt behavior in response to changes in the environment. Altered reward processing and impairments in cognitive flexibility are observed in psychiatric disorders such as obsessive compulsive disorder (OCD). Patients with this disorder show a disruption of functioning in the frontostriatal circuit and alterations in DA signaling. In this review we summarize findings from animal and human studies that have investigated the involvement of striatal DA in cognitive flexibility. These findings may provide a better understanding of the role of dopaminergic dysfunction in cognitive inflexibility in psychiatric disorders, such as OCD.