Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In keeping with previous observations in the CA1 and the somatosensory neocortex of the brain of rat, 20-min applications of 2-deoxy-D-glucose (2DG; 10 mM, replacing glucose) induced a long-term potentiation (LTP)-like enhancement of field excitatory synaptic potentials (fEPSPs) in the dentate region of hippocampal slices. The effects of 2DG were not identical at synapses of medial and lateral perforant paths (MPP and LPP). At MPP synapses, there was no post-2DG early depression of fEPSPs and the potentiation reached +78.6 +/- 5.7 % (+/- standard error of the mean) 40 min after the return to glucose. In the presence of 50 microM D-amino-phosphono valerate (APV; an N-methyl-D-aspartate [NMDA] receptor antagonist), a marked post-2DG depression appeared and the subsequent LTP was reduced to +34.7 +/- 2.8 % (for both 2DG- and APV-treatment P<0.001 by ANOVA-2W). At LPP synapses, even under control conditions, there was a sharp post-2DG depression followed by LTP (+62.2 +/- 5.7 %) and APV had little effect on either the post-2DG depression or LTP, reducing the latter by only 24 % [the 2DG treatment was very significant (P<0.001) but not the APV treatment]. Thus, 2DG evokes both NMDAR-dependent and -independent components of LTP in the perforant pathways. In view of these findings, the consumption of 2DG could have significant effects on synaptic plasticity and cognitive function.
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PMID:Two-deoxyglucose-induced long-term potentiation in slices of rat dentrate gyrus. 1772 7

Dentate granule cells receive inputs from the entorhinal cortex as the "perforant path". There are two components of the perforant path: the lateral component (LPP) and the medial component (MPP). LPP and MPP convey different sensory modality information. It remains elusive as to how signals from different inputs interact and integrate at the granule cell level. We attempted to address this issue by using nonlinear systems analytic methods. Granule cell EPSPs and action potentials were recorded intracellularly from in vitro hippocampal slices of the rat. MPP and LPP were activated simultaneously by two independent Poisson random trains. Poisson-Volterra kernel models were estimated using Laguerre expansion of Volterra kernel technique. In the kernel models, self-kernels represent the intrinsic input/output properties of each pathway, while cross-kernels quantify the interactions between the two inputs. Short-term plasticity (STP) was revealed by both 2nd order self and cross kernels. We reason that the underlying mechanisms of the STP are diffusely distributed along input-specific synapses, dendritic tree and soma. The plasticity held by the dendritic tree/soma and synapses can be divided and referred to as neuronal and synaptic plasticity respectively. We argue that the cross kernel properties are determined primarily by neuronal plasticity while the self kernel properties are controlled largely by synaptic plasticity. Our experimental data suggest that linear summation of the membrane potential of the postsynaptic neuron can only partially explain the neuronal plasticity. Both supra- and sublinear summations were observed. Thus, the neuronal plasticity is likely to be the product of passive and active processes of the postsynaptic neuron and plays a pivotal role in multiple inputs integration.
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PMID:Interaction of short-term neuronal plasticity and synaptic plasticity revealed by nonlinear systems analysis in dentate granule cells. 1794 14

It has been suggested that non-spatial and spatial pieces of information are transmitted to the dentate gyrus from entorhinal cortex layer II through the lateral and medial perforant paths (LPP and MPP), which establish synapses on granule cell dendrites in the outer and middle one-thirds of the dentate molecular layer, respectively. In the present paper, we first investigated cooperation and competition between MPP and LPP synapses being subject to STDP rules, using a four-compartmental granule cell model. MPP and LPP were stimulated simultaneously by periodic and random pulse trains, respectively. Both synapses were gradually enhanced by cooperation between those synapses in the early stage, and then either the MPP or the LPP synapse was rapidly enhanced through synaptic competition in the following stage, depending on their initial synaptic conductances. The dominant cause of synaptic competition is that the distance between the MPP synapse and the soma is shorter than that between the LPP synapse and the soma. These results suggest that the LPP and MPP synapses tend to be enhanced in the dentate supra- and infrapyramidal blades, respectively, taking account of the thickness of each of the LPP and MPP fiber laminae in the blades. The dentate gyrus may select spatial and non-spatial pieces of information through synaptic cooperation, and may open a gate for each piece of information through synaptic competition. Then we investigated the role of inhibitory local circuits in synaptic competition in the dentate gyrus. The feed-forward GABA(B) inhibition suppressed unusual high-frequency firing of the granule cell, and consequently prevented excessive synaptic depression due to synaptic competition through STDP. The feed-forward and feedback GABA(A) inhibitions tend to reduce synaptic conductance fluctuations resulting from large increments and decrements due to very small spike-timings happening occasionally.
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PMID:Cooperation and competition between lateral and medial perforant path synapses in the dentate gyrus. 2126 6

The entorhinal cortex (EC) is divided into medial (MEC) and lateral (LEC) anatomical areas, and layer II neurons of these two regions project to granule cells of the dentate gyrus through the medial and lateral perforant pathways (MPP and LPP), respectively. Stellate cells (SCs) represent the main neurons constituting the MPP inputs, while fan cells (FCs) represent the main LPP inputs. Here, we first characterized the excitability properties of SCs and FCs in adult wild-type (WT) mouse brain. Our data indicate that, during sustained depolarization, action potentials (APs) generated by SCs exhibit increased fast afterhyperpolarization and overshoot, making them able to fire at higher frequencies and to exhibit higher spike frequency adaptation (SFA) than FCs. Since the EC is one of the earliest brain regions affected during Alzheimer's disease (AD) progression, we compared SCs and FCs firing in 4-month-old WT and transgenic Tg2576 mice, a well-established AD mouse model. Tg2576-SCs displayed a slight increase in firing frequency during mild depolarization but otherwise normal excitability properties during higher stimulations. On the contrary, Tg2576-FCs exhibited a decreased firing frequency during mild and higher depolarizations, as well as an increased SFA. Our data identify the FCs as a neuronal population particularly sensitive to early pathological effects of chronic accumulation of APP-derived peptides, as it occurs in Tg2576 mice. As FCs represent the major input of sensory information to the hippocampus during memory acquisition, early alterations in their excitability profile could significantly contribute to the onset of cognitive decline in AD.
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PMID:Firing properties of entorhinal cortex neurons and early alterations in an Alzheimer's disease transgenic model. 2413 29


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