Correlation between Changes in Stress-Induced Corticosterone Secretion and GR mRNA Levels

The current study was conducted to determine the potential relationship between stress-induced corticosterone secretion and corticosteroid receptor mRNA levels after 5 days of intermittent stress. In particular, we were interested in the rate at which animals terminate a stress response, and how this termination may be altered by repeated stress. Adult male Sprague-Dawley rats were subjected to either 5 days of restraint stress or 5 days of an unpredictable stress paradigm. Restraint-stress induced corticosterone secretion was measured on Days 1 and 5 in both groups, and animals were killed on Day 6. Glucocorticoid receptor (GR), and mineralocorticoid (MR) mRNA levels were determined using in-situ hybridization techniques. Five days of restraint stress caused an habituation of the plasma corticosterone response to stress measured 60 and 90 min post-stress initiation; this pattern of corticosterone secretion was not observed in the animals subjected to unpredictable stress. Five days of either stress paradigm did not alter MR mRNA levels measured within the hippocampus or GR mRNA levels within the hippocampus or the medial parvocellular division of the paraventricular nucleus of the hypothalamus (mpPVN). However, an individual's GR mRNA levels measured within the CA1/2 region of the hippocampus and the mpPVN were significantly correlated with the degree of habituation of the corticosterone response to stress measured on Day 5. This suggests that an increase in the rate of termination of the stress response and levels of GR within the hippocampus and mpPVN may be functionally related.     

Differentiating challenge reactivity from psychomotor activity in studies of children's psychophysiology: considerations for theory and measurement

Current methods of assessing children’s physiological “stress reactivity” may be confounded by psychomotor activity, biasing estimates of the relation between reactivity and health. We examined the joint and independent contributions of psychomotor activity and challenge reactivity during a protocol for 5- and 6-year-old children (N = 338). Measures of parasympathetic reactivity (respiratory sinus arrhythmia [RSA]) and sympathetic reactivity (preejection period [PEP]) were calculated for social, cognitive, sensory, and emotional challenge tasks. Reactivity was calculated relative to both resting and a paired comparison task that accounted for psychomotor activity effects during each challenge. Results indicated that comparison tasks themselves elicited RSA and PEP responses, and reactivity adjusted for psychomotor activity was incongruent with reactivity calculated using rest. Findings demonstrate the importance of accounting for confounding psychomotor activity effects on physiological reactivity.     

Insulin receptor signaling in long-term memory consolidation following spatial learning

Evidence has shown that the insulin and insulin receptor (IR) play a role in cognitive function. However, the detailed mechanisms underlying insulin's action on learning and memory are not yet understood. Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus. After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region. These were correlated with a significant reduction in hippocampal IR protein levels. Learning-specific increases in levels of downstream molecules such as IRS-1 and Akt were detected in the synaptic membrane accompanied by decreases in Akt phosphorylation. Translocation of Shc protein to the synaptic membrane and activation of Erk1/2 were also observed after long-term memory formation. Despite the clear memory-correlated alterations in IR signaling pathways, insulin deficits in experimental diabetes mellitus (DM) rats induced by intraperitoneal injections of streptozotocin resulted in only minor memory impairments. This may be due to higher glucose levels in the DM brain, and to compensatory mechanisms from other signaling pathways such as the insulin-like growth factor-1 receptor (IGF-1R) system. Our results suggest that insulin/IR signaling plays a modulatory role in learning and memory processing, which may be compensated for by alternative pathways in the brain when an insulin deficit occurs.     

Pavlovian conditioning of distinct components of Hermissenda's responses to rotation

In two experiments with the nudibranch mollusk Hermissenda, distinct characteristics of conditioned and unconditioned responses to high-speed orbital rotation were examined. In Experiment 1, two principle unconditioned responses to rotation were identified, namely, reduced rate of locomotion and contraction of the foot. The magnitude of the foot contraction increased throughout a 20-s period of rotation, whereas locomotion was reduced immediately after the onset of the rotation and was maintained at this constant low rate throughout the stimulus presentation. These divergent response patterns suggest that the two responses emerge independently. In Experiment 2, a classical conditioning procedure was employed in which a light (CS) was paired with the rotation (US) employed in Experiment 1. In a subsequent test, it was found that the light had acquired the capability to evoke both foot contraction and decreased locomotion. Although the magnitude of these conditioned responses was reduced relative to the corresponding unconditioned response, the patterns of responding were virtually identical; that is, foot contraction developed gradually whereas locomotion decreased immediately. In contrast, animals that received unpaired presentations of the light and rotation, light alone, or no prior exposure to those stimuli exhibited foot extension in response to the light. These results illustrate a transfer of some of the response-evoking properties of the US to the CS as a result of conditioning, as well as the emergence of two independent conditioned responses. Moreover, these results suggest modulation of at least two distinct motor pathways as a function of learning.     

Two different biological configurations for long-term memory

Long-term memory (LTM) in Hermissenda can be distinguished from consolidated long-term memory (CLTM) by determining how long recall is retained. LTM is retained for approximately 1 day, while CLTM is retained for at least 3 days. During the transition from LTM to CLTM, the extent of retention appears to depend partially on how much consolidation has been completed. Several models are discussed that may be related to the two different manifestations of recall.     

Associatively reduced withdrawal from shadows in Hermissenda: a direct behavioral analog of photoreceptor responses to brief light steps

When the nudibranch Hermissenda crassicornis encounters a shadow in an otherwise uniformly illuminated field, it stops and turns back into the light within seconds. Associative conditioning, with paired light and rotation stimuli, produces learned modifications of phototaxis in illumination gradients. This same training procedure significantly reduced the ability of paired, but not random or naive control animals, to withdraw from shadows. In naive animals, after 13 min of dark adaptation, withdrawal from shadows was less apparent when animals encountered this stimulus the first time than after the second encounter. This difference in responsiveness to the first and second edge stimulus paralleled differences in type B photoreceptor impulse frequencies recorded during and after first and second steps of light. Earlier studies have shown that associative training of Hermissenda increases a long-lasting depolarization (LLD) which follows a light step. Our present findings suggest a functional relationship between the LLD of the type B photoreceptor and the behavioral response to light-dark differences. This supports the view that membrane changes which cause modifications of LLD magnitude store the learned association for later recall.     

Reduction of two voltage-dependent K+ currents mediates retention of a learned association

A single identified neuron, the medial type B photoreceptor, was isolated by axotomy from the nervous systems of nudibranch molluscs (Hermissenda) which had been exposed to three different training experiences. Paired animals had been trained with repeated paired presentations of light and rotation and random animals with randomized light and rotation; naive animals had no training. A two-microelectrode voltage clamp of axotomized type B somata (separated from all synaptic interactions and impulse activity) was used to measure, with a blind procedure, three distinct ionic currents at least 24 h after the training experience. An early K+ current, IA, and a Ca2+-dependent K+ current, ICa2+-K+, but not a light-induced inward Na+ current, were significantly reduced for the paired as compared to the random and naive animals. The magnitude of ICa2+-K+ reduction was related (again measured blindly) to the degree of training-induced suppression of phototaxis (a measure of the learned behavior) for the paired animals. These data are consistent with previous observations indicating that changes of intrinsic type B membrane properties are an important means for encoding the acquisition and retention of Hermissenda associative learning.     

Background illumination effects upon in vitro conditioning in Hermissenda

In the marine snail Hermissenda, associative learning can be accomplished by paired presentations of light and vestibular stimulation. It is generally assumed that associative learning depends upon the intensity or salience of the conditioned or unconditioned stimulus (CS and US, respectively). Accordingly, during Hermissenda conditioning a stronger dark adaptation is expected to render the CS (the light) more salient and hence facilitate association. We studied the influence of background illumination level using an in vitro pairing procedure in Hermissenda. This procedure allows one to assess the effect of conditioning upon a single cell, the B photoreceptor, which is implicated in this learning process. After 15 min of adaptation to a dim background light, B photoreceptors maintained a basal rate of firing, while after adaptation to complete darkness, they stopped firing. Paired and unpaired groups received 10 training trials in either a completely dark or a dim light environment. Although a trial to trial cumulative increase in excitability was found in the paired group trained in darkness, only the paired group trained under dim background light showed a higher input resistance and cell excitability 10 min after training. These results suggest that the background dim illumination was not needed for the induction but played a role in the maintenance of the pairing effect. Possible mechanisms for such a modulatory effect are discussed.