Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus. Restraint stress significantly increased the contents of all these neuropeptides in thymic, but not splenic, extracts. A single icv injection of IL-1beta increased contents of CRH, AVP, ACTH and beta-endorphin in the spleens of both sham-operated and adrenalectomised (ADX) rats. IL-1beta increased thymic contents of CRH and ACTH in sham-operated rats but these increases were not observed in ADX rats. These results suggest that the effects of IL-1beta on neuropeptide expression in the spleen are independent of glucocorticoids, whereas IL-1beta stimulation of neuropeptide expression in the thymus is dependent on circulating glucocorticoids. There were significant correlations between increases in CRH, ACTH and beta-endorphin in the spleen, and between CRH and ACTH in the thymus, consistent with the suggestion that IL-1beta-induced increases in ACTH and beta-endorphin may be mediated through CRH. These results provide evidence that stressors can directly influence neuropeptide expression in immune tissues. Thus stress may influence immune functions through paracrine mechanisms involving locally synthesised neuropeptides as well as through activation of the hypothalamo-pituitary-adrenal axis.     

Coincident induction of long-term facilitation at sensory-motor synapses in Aplysia: presynaptic and postsynaptic factors

Induction of long-term synaptic changes at one synapse can facilitate the induction of long-term plasticity at another synapse. Here we show that if Aplysia sensory neuron (SN) somata and their remote motor neuron (MN) synapses are simultaneously exposed to serotonin (5HT) pulses, which at either site alone are insufficient to induce long-term facilitation (LTF), processes activated at these sites interact to induce LTF. Coincident induction of LTF requires: (1) that the synaptic pulse occurs within a brief temporal window of the somatic pulse and (2) that local protein synthesis occurs immediately at the synapse, followed by delayed protein synthesis at the soma. LTF at the SN-MN synapses can also be induced with cell-wide application of repeated pulses of 5HT. However, these two forms of LTF differ mechanistically: (1) coincident LTF requires protein synthesis in the postsynaptic motor neuron, whereas repeated 5HT LTF does not, and (2) repeated 5HT LTF is accompanied by intermediate-term (3 h) facilitation, whereas coincident LTF is not. Thus LTF expressed in the same temporal domain can result from different underlying mechanisms.     

The tail-elicited tail withdrawal reflex of Aplysia is mediated centrally at tail sensory-motor synapses and exhibits sensitization across multiple temporal domains

The defensive withdrawal reflexes of Aplysia californica have provided powerful behavioral systems for studying the cellular and molecular basis of memory formation. Among these reflexes the tail-elicited tail withdrawal reflex (T-TWR) has been especially useful. In vitro studies examining the monosynaptic circuit for the T-TWR, the tail sensory-motor (SN-MN) synapses, have identified the induction requirements and molecular basis of different temporal phases of synaptic facilitation that underlie sensitization in this system. They have also permitted more recent studies elucidating the role of synaptic and nuclear signaling during synaptic facilitation. Here we report the development of a novel, compartmentalized semi-intact T-TWR preparation that allows examination of the unique contributions of processing in the SN somatic compartment (the pleural ganglion) and the SN-MN synaptic compartment (the pedal ganglion) during the induction of sensitization. Using this preparation we find that the T-TWR is mediated entirely by central connections in the synaptic compartment. Moreover, the reflex is stably expressed for at least 24 h, and can be modified by tail shocks that induce sensitization across multiple temporal domains, as well as direct application of the modulatory neurotransmitter serotonin. This preparation now provides an experimentally powerful system in which to directly examine the unique and combined roles of synaptic and nuclear signaling in different temporal domains of memory formation.     

Hypothalamo-Pituitary-Adrenocortical Regulation Following Lesions of the Central Nucleus of the Amygdala

Previous reports indicate that the central nucleus of the amygdala (CeA) stimulates adrenocorticotropin and corticosterone secretion, suggesting a role for this region in central hypothalamo-pituitary-adrenocortical (HPA) stress regulation. To evaluate this hypothesis, this study assessed the impact of CeA lesion on the response of hypophysiotrophic paraventricular nucleus (PVN) neurons to acute restraint and chronic unpredictable stress exposure. In contrast to previous reports, CeA lesions did not affect corticosterone or ACTH secretion induced by acute stress. Acute restraint increased PVN corticotropin releasing hormone (CRH) mRNA expression, increased the number of parvocellular PVN neurons expressing the co-secretagogue arginine vasopressin (AVP), and induced cFOS mRNA expression in the parvocellular PVN. However, there was no additional effect of CeA lesion on any measure of PVN activation. Chronic unpredictable stress exposure induced long-term activation of the HPA axis, noted by thymic involution, adrenal hypertrophy and increased PVN CRH mRNA expression. Stress-induced changes in thymus and adrenal weights were not affected by CeA lesion. Further, CeA lesion rats did not differ from controls in post-stress CRH mRNA expression. However, basal CRH mRNA expression was increased in the PVN of CeA rats, suggesting that the CeA plays a role in long-term inhibition of the PVN. The results of these studies are not consistent with the hypothesis that the CeA is necessary for stress-induced pituitary-adrenocortical activation. Rather, this region may play a stressor-specific modulatory role in regulation of HPA function.     

Differential Induction of Long-Term Synaptic Facilitation by Spaced and Massed Applications of Serotonin at Sensory Neuron Synapses of Aplysia californica

Serotonin (5HT)-induced facilitation of synaptic transmission from tail sensory neurons (SNs) to motor neurons (MNs) in the marine mollusc Aplysia provides a cellular model of short- and long-term memory for behavioral sensitization of the tail withdrawal reflex. Synaptic facilitation at these synapses occurs in three temporal phases: short-term (STF, lasting minutes), intermediate-term (ITF, lasting more than an hour), and long-term (LTF, lasting >24 hr). STF, ITF, and LTF differ in their induction requirements: A single brief exposure of 5HT induces STF, whereas five applications are required for ITF and LTF. Moreover, STF and LTF can be induced independently.