A large-scale detailed neuronal model of electrical stimulation of the dentate gyrus and perforant path as a platform for electrode design and optimization

Author(s):  
Clayton S. Bingham ◽  
Kyle Loizos ◽  
Gene Yu ◽  
Andrew Gilbert ◽  
Jean-Marie Bouteiller ◽  
...  
2008 ◽  
Vol 86 (5) ◽  
pp. 249-256 ◽  
Author(s):  
Takashi Kubota ◽  
Itsuki Jibiki ◽  
Akira Ishikawa ◽  
Tomomi Kawamura ◽  
Sonoko Kurokawa ◽  
...  

We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine’s clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path–dentate gyrus pathway.


1997 ◽  
Vol 77 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Valérie Doyère ◽  
Bolek Srebro ◽  
Serge Laroche

Doyère, Valérie, Bolek Srebro, and Serge Laroche. Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J. Neurophysiol. 77: 571–578, 1997. We examined the characteristics of heterosynaptic long-term depression (LTD) and depotentiation of previously established long-term potentiation (LTP) in the medial and lateral entorhinal afferents to the dentate gyrus in the awake rat. Rats were prepared for chronic recording of dentate gyrus evoked potentials to activation of the medial and lateral perforant paths. This study in awake rats confirms that heterosynaptic LTD can be induced at inactive medial perforant path synapses in conjunction with the induction of LTP produced by high-frequency stimulation of the lateral perforant path. This form of LTD was long lasting and reversible by tetanic stimulation delivered to the depressed pathway. In contrast, tetanic stimulation of the medial perforant path had only a small heterosynaptic effect on the lateral pathway, suggesting that the two input pathways to the dentate gyrus are not symmetrical in their ability to induce heterosynaptic LTD. We also examined the ability of high-frequency stimulation of one pathway to produce depotentiation of the other pathway. We found that when LTP was first induced in the medial perforant path, depotentiation was induced heterosynaptically by tetanization of the lateral pathway. Both newly established LTP (30 min) and LTP induced and saturated by repeated tetanic stimulation over several days can be depotentiated heterosynaptically. Moreover, depotentiation of the medial perforant path synapses was found to be linearly correlated with the magnitude of LTP induced in the lateral perforant path synapses, and subsequent tetanic stimulation of the depotentiated medial perforant path restored LTP to an extent that counterbalanced depotentiation. The saturation and repotentiation experiments provide clear support for the conclusion that the rapid reversal of LTP reflects true depotentiation of the medial input. Again, as with heterosynaptic LTD, tetanization of the medial perforant path had little effect on previously induced LTP in the lateral path. These results provide evidence that medial perforant path synapses can be depressed and depotentiated heterosynaptically. They suggest that in the intact rat synaptic changes in the afferents to the dentate gyrus from the lateral entorhinal cortex exert powerful control over ongoing or recent synaptic plasticity in the medial entorhinal afferents.


2020 ◽  
Vol 21 (11) ◽  
pp. 3786 ◽  
Author(s):  
Rose-Marie Vouimba ◽  
Rachel Anunu ◽  
Gal Richter-Levin

The term “metaplasticity” is used to describe changes in synaptic plasticity sensitivity following an electrical, biochemical, or behavioral priming stimulus. For example, priming the basolateral amygdala (BLA) enhances long-term potentiation (LTP) in the dentate gyrus (DG) but decreases LTP in the CA1. However, the mechanisms underlying these metaplastic effects are only partly understood. Here, we examined whether the mechanism underlying these effects of BLA priming involves intra-BLA GABAergic neurotransmission. Low doses of muscimol, a GABAA receptor (GABAAR) agonist, were microinfused into the rat BLA before or after BLA priming. Our findings show that BLA GABAAR activation via muscimol mimicked the previously reported effects of electrical BLA priming on LTP in the perforant path and the ventral hippocampal commissure-CA1 pathways, decreasing CA1 LTP and increasing DG LTP. Furthermore, muscimol application before or after tetanic stimulation of the ventral hippocampal commissure-CA1 pathways attenuated the BLA priming-induced decrease in CA1 LTP. In contrast, muscimol application after tetanic stimulation of the perforant path attenuated the BLA priming-induced increase in DG LTP. The data indicate that GABAAR activation mediates metaplastic effects of the BLA on plasticity in the CA1 and the DG, but that the same GABAAR activation induces an intra-BLA form of metaplasticity, which alters the way BLA priming may modulate plasticity in other brain regions. These results emphasize the need for developing a dynamic model of BLA modulation of plasticity, a model that may better capture processes underlying memory alterations associated with emotional arousing or stressful events.


2007 ◽  
Vol 75 (2-3) ◽  
pp. 154-161 ◽  
Author(s):  
Mohammad Mohammad-Zadeh ◽  
Javad Mirnajafi-Zadeh ◽  
Yaghoub Fathollahi ◽  
Mohammad Javan ◽  
Parviz Ghorbani ◽  
...  

1983 ◽  
Vol 61 (10) ◽  
pp. 1156-1161 ◽  
Author(s):  
R. W. Skelton ◽  
J. J. Miller ◽  
A. G. Phillips

Brief periods of high-frequency stimulation of hippocampal afferents produce long-term potentiation (LTP) of synaptic transmission, but the minimum frequency capable of inducing this alteration in synaptic efficacy has not been specified. The present study used the repeated measurement of input–output curves in the perforant path – dentate gyrus system of freely moving rats to monitor synaptic efficacy and found that stimulation at 0.2 Hz, but not 0.04 Hz produced LTP. These results suggest that the minimum stimulation frequency capable of producing LTP is lower than previously described. Possible reasons for the discrepancy between the present and previous findings are discussed, along with the implications of low-frequency potentiation.


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