Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine general or species-specific properties in neural systems, it is necessary to use comparative data in evaluating experimental findings. Presented here are data on associative learning and memory formation in honeybees, emphasizing a comparative approach. We focus on four aspects: (1) the role of an identified neuron, VUM(mx1), as a neural substrate of appetitive reinforcement; (2) the sequences of molecular events as they correlate with five forms of memory stages; (3) the localization of the memory traces following appetitive olfactory learning; and (4) the brief description of several forms of complex learning in bees (configuration in olfactory conditioning, categorization in visual feature learning, delayed matching-to-sample learning, and latent learning in navigation). VUM(mx1) activity following the conditioned stimulus odor is sufficient to replace the unconditioned stimulus, and VUM(mx1) changes its response properties during learning similarly to what is known from dopamine neurons in the basal ganglia of the mammalian brain. The transition from short- to mid- and long-term forms of memory can be related to specific activation of second messenger cascades (involving NOS, PKA, PKC, and PKM) resembling general features of neural plasticity at the cellular level. The particular time course of the various memory traces may be adapted to the behavioral context in which they are used; here, the foraging cycle of the bee. Memory traces for even such a simple form of learning as olfactory conditioning are multiple and distributed, involving first- and second-order sensory neuropils (antennal lobe and mushroom bodies), but with distinctly different properties. The wealth of complex forms of learning in the context of foraging indicates basic cognitive capacities based on rule extraction and context-dependent learning. It is believed that bees might be a useful model for studying cognitive faculties at a middle level of complexity.
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PMID:Searching for the memory trace in a mini-brain, the honeybee. 1127 50

The conditioned taste aversion (CTA) paradigm was used to assess the role of Ca(2+)/calmodulin-dependent protein kinase (CAMKII) in associative learning. KN62, a specific inhibitor of CAMKII, was injected into the parabrachial nuclei (PBN) either immediately after saccharin drinking (CS) or after saccharin drinking and i.p. injection of LiCl (US). Injection of KN62 into the PBN after saccharin drinking elicited clear CTA (Exp. 1). This effect was dosage-dependent and site-specific (Exp. 2). The results are discussed in relation with an earlier report showing that CTA acquisition is disrupted by injection of Ca(2+)/phospholipid-dependent protein kinase (PKC) inhibitor chelerythrine into the PBN during CS-US interval. It is suggested that the principal serine/threonine kinases play different roles in CTA learning: whereas PKC activity is necessary for the gustatory short-term memory formation, CAMKII acts similarly to the US itself-an unexpected role of CAMKII in associative learning.
Neurobiol Learn Mem 2001 May
PMID:CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion in rats. 1130 Jul 32

We have sought to elucidate the biochemical mechanisms that underlie the memory enhancing properties of the neural peptide vasopressin. Toward that goal we have investigated vasopressin induction of calcium signaling cascades, long held to be involved in long-term memory function, in neurons derived from the cerebral cortex, a brain region associated with long-term memory. Our previous studies demonstrated that in cultured cortical neurons, V1a vasopressin receptor (V1aR) activation resulted in a sustained rise in intracellular calcium concentration that was dependent on calcium influx (Son & Brinton, 1998). To investigate the mechanism of V1aR-induced calcium influx, we investigated V1aR activation of the calcium channel subtype(s) in cortical neurons cultured from Sprague-Dawley rat embryonic day 18 fetuses. The results of these analyses demonstrated that the L-type calcium channel blocker nifedipine blocked 250 nM V1 vasopressin receptor agonist (V1 agonist)-induced calcium influx. Intracellular calcium imaging analyses using fura-2AM demonstrated that blockade of L-type calcium channels prevented the 250 nM V1 agonist-induced rise in intracellular calcium concentration. These results indicate that the influx of extracellular calcium via L-type calcium channels is an essential step in the initiation of the V1 agonist-induced rise in intracellular calcium concentration. To determine the mechanism of V1aR activation of L-type calcium channels, regulatory components of the phosphatidylinositol signaling pathway were investigated. The results of these analyses demonstrated that V1 agonist-induced calcium influx was blocked by both a phospholipase C inhibitor (U-73122) and a protein kinase C inhibitor (bisindolylmaleimide I). Further analysis of V1aR activation of protein kinase C (PKC) demonstrated that V1 agonist induced PKC activity within 1 min of exposure in cultured cortical neurons. These data indicate that in cultured cortical neurons, V1aR activation regulates the influx of extracellular calcium via L-type calcium channel activation through a protein kinase-C-dependent mechanism. The results of these studies provide biochemical mechanisms by which vasopressin could enhance memory function. Those mechanisms include a complex cascade that is initiated by activation of the phosphatidylinositol pathway, activation of protein kinase C, followed by phosphorylation of L-type calcium channels to initiate the influx of extracellular calcium to activate a cascade of calcium-dependent release of intracellular calcium.
Neurobiol Learn Mem 2001 Nov
PMID:Regulation and mechanism of L-type calcium channel activation via V1a vasopressin receptor activation in cultured cortical neurons. 1172 44

This article explores the causal and correlative relationships between kinases and learning and memory. Specifically, the contributions of three kinases-protein kinase A (PKA), calcium calmodulin-dependent kinase II (CaMKII), and protein kinase C (PKC)-are assessed during the consolidation phase of avoidance conditioning. The following sources of evidence are considered: inhibitor data, activity monitoring, and transgenic studies. An exhaustive effort is made to address several issues regarding the participation of these kinases in (a) posttraining timing and magnitude, (b) location across many brain regions, and (c) the use of multiple pharmacological agents and assays. In addition, this article attempts to integrate the behavioral data with the purported role of kinases in long-term potentiation (LTP).
Neurobiol Learn Mem 2002 May
PMID:The role of PKA, CaMKII, and PKC in avoidance conditioning: permissive or instructive? 1199 59

Learning and long-term memory are thought to involve temporally defined changes in gene expression that lead to the strengthening of synaptic connections in selected brain regions. We used cDNA microarrays to study hippocampal gene expression in animals trained in a spatial discrimination-learning paradigm. Our analysis identified 19 genes that showed statistically significant changes in expression when comparing Nai;ve versus Trained animals. We confirmed the changes in expression for the genes encoding the nuclear protein prothymosin(alpha) and the delta-1 opioid receptor (DOR1) by Northern blotting or in situ hybridization. In additional studies, laser-capture microdissection (LCM) allowed us to obtain enriched neuronal populations from the dentate gyrus, CA1, and CA3 subregions of the hippocampus from Nai;ve, Pseudotrained, and spatially Trained animals. Real-time PCR examined the spatial learning specificity of hippocampal modulation of the genes encoding protein kinase B (PKB, also known as Akt), protein kinase C(delta) (PKC(delta)), cell adhesion kinase(beta) (CAK(beta), also known as Pyk2), and receptor protein tyrosine phosphatase(zeta/beta) (RPTP(zeta/beta)). These studies showed subregion specificity of spatial learning-induced changes in gene expression within the hippocampus, a feature that was particular to each gene studied. We suggest that statistically valid gene expression profiles generated with cDNA microarrays may provide important insights as to the cellular and molecular events subserving learning and memory processes in the brain.
Neurobiol Learn Mem 2003 Jul
PMID:Hippocampal gene expression profiling in spatial discrimination learning. 1273 36

The neurotransmitter serotonin (5-HT) plays an important role in memory encoding in Aplysia. Early evidence showed that during sensitization, 5-HT activates a cyclic AMP-protein kinase A (cAMP-PKA)-dependent pathway within specific sensory neurons (SNs), which increases their excitability and facilitates synaptic transmission onto their follower motor neurons (MNs). However, recent data suggest that serotonergic modulation during sensitization is more complex and diverse. The neuronal circuits mediating defensive reflexes contain a number of interneurons that respond to 5-HT in ways opposite to those of the SNs, showing a decrease in excitability and/or synaptic depression. Moreover, in addition to acting through a cAMP-PKA pathway within SNs, 5-HT is also capable of activating a variety of other protein kinases such as protein kinase C, extracellular signal-regulated kinases, and tyrosine kinases. This diversity of 5-HT responses during sensitization suggests the presence of multiple 5-HT receptor subtypes within the Aplysia central nervous system. Four 5-HT receptors have been cloned and characterized to date. Although several others probably remain to be characterized in molecular terms, especially the Gs-coupled 5-HT receptor capable of activating cAMP-PKA pathways, the multiplicity of serotonergic mechanisms recruited into action during learning in Aplysia can now be addressed from a molecular point of view.
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PMID:Multiple serotonergic mechanisms contributing to sensitization in aplysia: evidence of diverse serotonin receptor subtypes. 1455 10

The nucleus accumbens (NAcc) has been shown to play a role in motor and spatial learning. Protein kinase C (PKC) has been implicated in the mechanisms of initiation and maintenance of long-term potentiation that is thought to be involved in the storage of long-term memory. In the present study, the importance of de novo synthesis of PKC-gamma within the NAcc in the acquisition and retention of spatial discrimination learning was assessed using an antisense knockdown approach. Separate groups of Long-Evans rats were exposed to acute microinfusions (6microg/microl) of PKC-gamma antisense oligodeoxynucleotide (AS-ODN), control oligodeoxynucleotide (C-ODN) or vehicle into the NAcc at 24 and 3h before each training session. Behavioral findings showed that the blockade of NAcc-PKC-gamma translation caused impairments in the early phase of learning and retention of spatial information. Biochemical experiments showed that PKC-gamma expression was reduced and Ca(2+)/phospholipid-dependent protein kinase C (PKC) activity was blocked significantly in the AS-ODN-treated rats in comparison with control rats. The present findings suggest that NAcc-PKC-gamma plays a role during the early acquisition of spatial learning. Also, retention test results suggest that NAcc-PKC-gamma may be working as an intermediate factor involved in the onset of molecular mechanisms necessary for spatial memory consolidation within the NAcc.
Neurobiol Learn Mem 2004 Mar
PMID:Spatial learning in rats is impaired by microinfusions of protein kinase C-gamma antisense oligodeoxynucleotide within the nucleus accumbens. 1499 Feb 32

ATP increased the PLD activity of rat submandibular ductal cells in a concentration-dependent and calcium-sensitive manner. Among ATP analogs, BZATP and ATPgammaS were the only ones able to stimulate the PLD activity. ATP and BZ-ATP also activated PLD in control mice, but not in mice lacking the P2X7 receptors. Oxidized ATP, Coomassie blue, NiCl2 and MgCl2 inhibited the response to ATP. PLD stimulation by ATP was inhibited by calphostin C and chelerythrine, two PKC inhibitors. The PLD stimulation by BZ-ATP and TPA, a phorbol ester which activates PKC, were not additive. Purinergic agonists did not increase the phosphorylation of proteins on tyrosyl residues. We can conclude that the activation of P2X7 receptors in rat submandibular glands ductal cells, is coupled to the activation of PLD. This activation is partly mediated by PKC and is not secondary to the activation of a tyrosine kinase.
Bull Mem Acad R Med Belg 2003
PMID:[Regulation by ATP of a phospholipase D in the ductal cells of the submaxillary gland]. 1502 72

Synaptic plasticity is thought to contribute to memory formation. Serotonin-induced facilitation of sensory-motor (SN-MN) synapses in Aplysia is an extensively studied cellular analog of memory for sensitization. Serotonin, a modulatory neurotransmitter, is released in the CNS during sensitization training, and induces three temporally and mechanistically distinct phases of SN-MN synaptic facilitation. The role of protein kinase A and protein kinase C in SN-MN synaptic facilitation is well documented. Recently, it has become clear that mitogen-activated protein kinase (MAPK) cascades also play a critical role in SN-MN plasticity. Here, we summarize the roles of MAPK cascades in synaptic plasticity and memory for sensitization in Aplysia.
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PMID:The roles of MAPK cascades in synaptic plasticity and memory in Aplysia: facilitatory effects and inhibitory constraints. 1528 79

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the intracellular events activated by their receptors that influence working memory are poorly understood. We demonstrate that working memory involves transient changes in prefrontal G(q/11)-signaling and in calcium-dependent intracellular protein phosphatase and kinase activity. Interestingly, inhibition of the calcium activated phosphatase calcineurin impaired, while calcium/calmodulin dependent kinase II (CaMKII) and calcium-dependent protein kinase C (PKC) enhanced, working memory. Our findings suggest that the active maintenance of information required for working memory involves transient changes in the balance of these enzymes' activities.
Learn Mem
PMID:A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory. 1580 9


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