Biomedical subjects

Volker Korz

Publications and source records attributed to Volker Korz.

7 recordsLinked to original sources

PubMed2006

Long-term effects of brief acute stress on cellular signaling and hippocampal LTP.

In a previous study, we reported that a brief exposure to swim stress transforms an electrically induced, protein synthesis-independent early long-term potentiation (early LTP) into a protein synthesis-dependent late LTP ["reinforcement of LTP" in the hippocampal dentate gyrus (DG)] (Korz and Frey, 2003). This transformation depends on activation of mineralocorticoid receptors (MRs) by corticosterone, and on intact basolateral amygdala (BLA) function. Here, we demonstrate that a brief swim experience results in lasting changes in levels of hippocampal cellular signaling molecules that are known to be involved in the induction of late LTP. Within the DG, MRs were rapidly upregulated, whereas glucocorticoid receptor (GR) levels were elevated with a 3 h delay. Levels of phosphorylated mitogen-activated protein kinase 2 (pMAPK2) and p38 MAPK, as well as phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMKII) were enhanced shortly after swim stress and remained elevated until 24 h, whereas levels of phosphorylated cAMP response element-binding protein (pCREB) remained unchanged. MR and GR were upregulated with a longer delay within the CA1 region, whereas levels of pMAPK2 and p38MAPK were rapidly increased, but the former returned to basal levels after 3 h. Levels of pCREB and pCaMKII were maintained in an enhanced state after swim stress. DG-LTP reinforcement requires a serotonergic but not dopaminergic heterosynaptic receptor activation that probably mediates the BLA-dependent modulation of LTP under stress. Thus, molecular alterations induced by specific stress resemble late LTP-related molecular changes. These changes, in interaction with stress-specific heterosynaptic processes, may support the transformation of early LTP into late LTP. The results contribute to the understanding of the rapid consolidation of cellular and possibly systemic memories triggered by stress.

Animals↗

PubMed2006

Water maze swim path analysis based on tracking coordinates.

In the Morris water maze, a task widely used to study spatial learning and memory in laboratory rodents, several parameters are employed to estimate cognitive abilities of animals by analyzing their swim path characteristics. An isolated view based on any one of these parameters is not always satisfactory, so multivariate procedures (factor analyses) are used to weight the parameters in context with the others. This method sheds light on some subtle differences in experimental animals' spatial memories or strategies. However, this approach has some subjective problems, because the definition of the parameters depends on the experimenter's opinion of appropriate measures; therefore, we suggest a bottom-up rather than a top-down analysis of swim paths by means of spatial coordinates. In the present study, swim paths were normalized to 100-element vectors and then subjected to a principal components analysis. Swim paths could be sufficiently described in terms of only three components, each of which accounted for specific characteristics of the trajectories. We found significant differences in swim path patterns between test groups of rats that could not be discriminated via standard water maze parameters. Thus, the components can be related to different aspects of spatial cognition not detectable by commonly used parameters.

Animals↗

PubMed2005

Bidirectional modulation of hippocampal long-term potentiation under stress and no-stress conditions in basolateral amygdala-lesioned and intact rats.

Hippocampal long-term potentiation (LTP) is widely considered as a cellular model for learning and memory formation. We have shown previously that protein synthesis-independent, early dentate gyrus (DG) LTP, lasting approximately 4-5 h, can be transformed into a late-LTP with a duration of > or = 24 h by a brief acute swim stress experience (high-stress condition). This reinforcement requires the activation of mineralocorticoid receptors and protein synthesis. The basolateral amygdala (BLA) is known to modulate glucocorticoid effects on the consolidation of spatial/contextual memory via a beta-adrenergic mechanism. Interestingly, hippocampal DG-LTP can also be indirectly modulated by beta-adrenergic and cholinergic/muscarinergic processes. Here, we show that the reinforcement of early-DG-LTP under high-stress conditions depends on the processing of novel spatial/contextual information. Furthermore, this reinforcement was blocked in BLA-lesioned animals compared with sham-operated and intact controls; however, it was not dependent on beta-adrenergic or cholinergic/muscarinergic receptor activation. In contrast, under low-stress conditions, the induction of late-LTP in BLA-lesioned animals is facilitated, and this facilitation, again, was dependent on beta-adrenergic activation. The data suggest that DG-LTP maintenance can be influenced by the BLA through different mechanisms: a short-lasting corticosterone-dependent and beta-adrenergic-independent mechanism and a long-lasting mechanism that facilitated hippocampal beta-adrenergic mechanisms.

Amygdala↗

PubMed2005

Reinforcement of rat hippocampal LTP by holeboard training.

Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4-5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be transformed (reinforced) into late-LTP by the association of arousing novel environmental stimuli. Here we show that consolidation of spatial memory also reinforces early-LTP in the dentate gyrus. Both memory consolidation and LTP-reinforcement depend on protein synthesis. Four groups of animals were trained by five, seven, eight or 10 trials, respectively, to recognize a fixed pattern of baited holes. The last trial was performed 15 min after tetanus. Errors of long-term reference memory during the last trial were significantly decreased only in the eight- and 10-trial experimental groups compared to pseudo-trained animals. In correlation to this learning effect we found a reinforcement of early-LTP only in these experimental groups compared to controls. The data suggest that the synthesis of new proteins required for spatial reference-memory formation also contributes to LTP maintenance in the hippocampal dentate gyrus.

Animals↗

PubMed2003

Requirement of beta-adrenergic receptor activation and protein synthesis for LTP-reinforcement by novelty in rat dentate gyrus.

Long-term potentiation (LTP) is supposed to be a cellular mechanism involved in memory formation. Similar to distinct types of memory formation, LTP can be separated into a protein synthesis-independent early phase (early-LTP) and a protein synthesis-dependent late phase (late-LTP). An important question is whether the transformation from early- into late-LTP can be elicited by behavioural conditions such as the attention to novel events. Therefore, we investigated the effect of exploration of a novel environment (novelty-exploration) on subsequently induced early-LTP in the dentate gyrus of freely moving rats. While a delay of 60 min between exploration onset and LTP induction had no effect, intervals of 30 or 15 min led to a reinforcement of early- to late-LTP. Exploration of a familiar environment failed to prolong LTP maintenance. The novelty-induced LTP reinforcement was blocked when the translation inhibitor anisomycin or the beta-adrenergic antagonist propranolol were applied intracerebroventricularly before exploration onset. These findings support the hypothesis that the synergistic interplay of novelty-triggered noradrenergic activity and weak tetanic stimulation promotes the synthesis of certain proteins that are required for late-LTP. Such a cellular mechanism may underlie novelty-dependent enhancement of memory formation.

Animals↗

PubMed2003

Stress-related modulation of hippocampal long-term potentiation in rats: Involvement of adrenal steroid receptors.

Stress is usually correlated with an increased release of glucocorticoids from the adrenal glands. Within the hippocampus, a structure long known to be involved in spatial learning, two corticosterone-binding receptors are identified: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Activation of these receptors impairs or facilitates hippocampal long-term potentiation (LTP), respectively. Stress elicited by behavioral manipulations may interfere with cognitive modulations of LTP during learning experiments. Here, we explore the influence of two stress-inducing procedures, handling and swimming, on the maintenance of dentate gyrus LTP in the rat induced by a weak tetanization of the perforant path. Manipulations started 15 min after tetanization. Handling alone resulted in a complete reversal of LTP. Handling followed by a 2 min swim in a water tank elicited prolonged protein synthesis but not beta-adrenergic-dependent LTP compared with either control or handled animals. Blockade of the GRs but not of the MRs prevented the reversal of LTP by handling. Inactivation of the MRs but not of the GRs hindered LTP prolongation by swimming. Because the activated receptor complexes act as transcription factors, MR- and GR-related proteins may play a role in the maintenance of LTP. The data suggest a complex interplay of corticosterone-binding receptors on modulations of hippocampal LTP and thus, of stress on learning and functional plasticity in general.

Adrenal Glands↗

PubMed2003

Bidirectional modulation of long-term potentiation by novelty-exploration in rat dentate gyrus.

Previous studies have shown that exploration of a novel environment reverses hippocampal long-term potentiation (LTP). Here we demonstrate a bidirectional modulation of LTP measured in the dentate gyrus of freely moving rats by means of novelty exploration. A transient form of LTP lasting about 6 h was induced in perforant path-granular cell-synapses by a weak tetanization protocol (three bursts of 15 pulses at f=200 Hz). LTP was reversed when non-restricted exploration of a novel environment started 2 min after LTP induction. In contrast, using the same interval and limiting the exploration duration to 1 min led to LTP-prolongation. Furthermore, LTP-reinforcement was also obtained when a not-restricted exploration started within 2 min before tetanization. The observed interplay of LTP-impairing and -enhancing factors may be relevant for the modulation of memory formation by novelty.

Animals↗