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Entorhinal denervation induces homeostatic synaptic scaling of excitatory postsynapses of dentate granule cells in mouse organotypic slice cultures.

Vlachos A, Becker D, Jedlicka P, Winkels R, Roeper J, Deller T - PLoS ONE (2012)

Bottom Line: Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength.To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin.By using computational modeling and local electrical stimulations in Strontium (Sr(2+))-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3-4 days post lesion.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Frankfurt, Germany. a.vlachos@med.uni-frankfurt.de

ABSTRACT
Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥ 3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr(2+))-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3-4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro.

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Denervation induces homeostatic synaptic scaling.(A, B) Treatment of denervated cultures with the sodium channel blocker tetrodotoxin (A; TTX 2 µM, 2 d) did not significantly change the denervation-induced compensatory increase in excitatory synaptic strength (B; n = 5 cultures per group), indicating that granule cells utilize, at least in part, similar mechanisms to adjust their excitatory synaptic strength in a homeostatic manner following denervation and TTX-treatment.
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pone-0032883-g003: Denervation induces homeostatic synaptic scaling.(A, B) Treatment of denervated cultures with the sodium channel blocker tetrodotoxin (A; TTX 2 µM, 2 d) did not significantly change the denervation-induced compensatory increase in excitatory synaptic strength (B; n = 5 cultures per group), indicating that granule cells utilize, at least in part, similar mechanisms to adjust their excitatory synaptic strength in a homeostatic manner following denervation and TTX-treatment.

Mentions: A well established method to perturb neuronal activity and to induce homeostatic synaptic scaling is chronic blockade of sodium channels with TTX (e.g., [17]–[23]). We therefore combined denervation and TTX-treatment to test whether these two experimental conditions exploit, at least in part, similar mechanisms. A comparable approach to test for homeostatic synaptic scaling has been reported previously [24], [25]. If similar mechanisms are involved, we hypothesized that TTX should have no effect, or at least a smaller effect on mean mEPSC amplitude of denervated granule cells in comparison to non-denervated granule cells. If the underlying mechanisms are dissimilar, we expected that denervation and TTX should have an additive effect on granule cell mEPSC amplitudes. As shown in Figure 3, treatment of non-lesioned control cultures with 2 µM TTX for 2 d induced a significant increase in mEPSC amplitude, suggesting that dentate granule cells show robust synaptic up-scaling. The combination of denervation and TTX had no additive effect on the mean mEPSC amplitude (Figure 3; n = 5 cultures per group, 3–4 neurons recorded per culture).


Entorhinal denervation induces homeostatic synaptic scaling of excitatory postsynapses of dentate granule cells in mouse organotypic slice cultures.

Vlachos A, Becker D, Jedlicka P, Winkels R, Roeper J, Deller T - PLoS ONE (2012)

Denervation induces homeostatic synaptic scaling.(A, B) Treatment of denervated cultures with the sodium channel blocker tetrodotoxin (A; TTX 2 µM, 2 d) did not significantly change the denervation-induced compensatory increase in excitatory synaptic strength (B; n = 5 cultures per group), indicating that granule cells utilize, at least in part, similar mechanisms to adjust their excitatory synaptic strength in a homeostatic manner following denervation and TTX-treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293910&req=5

pone-0032883-g003: Denervation induces homeostatic synaptic scaling.(A, B) Treatment of denervated cultures with the sodium channel blocker tetrodotoxin (A; TTX 2 µM, 2 d) did not significantly change the denervation-induced compensatory increase in excitatory synaptic strength (B; n = 5 cultures per group), indicating that granule cells utilize, at least in part, similar mechanisms to adjust their excitatory synaptic strength in a homeostatic manner following denervation and TTX-treatment.
Mentions: A well established method to perturb neuronal activity and to induce homeostatic synaptic scaling is chronic blockade of sodium channels with TTX (e.g., [17]–[23]). We therefore combined denervation and TTX-treatment to test whether these two experimental conditions exploit, at least in part, similar mechanisms. A comparable approach to test for homeostatic synaptic scaling has been reported previously [24], [25]. If similar mechanisms are involved, we hypothesized that TTX should have no effect, or at least a smaller effect on mean mEPSC amplitude of denervated granule cells in comparison to non-denervated granule cells. If the underlying mechanisms are dissimilar, we expected that denervation and TTX should have an additive effect on granule cell mEPSC amplitudes. As shown in Figure 3, treatment of non-lesioned control cultures with 2 µM TTX for 2 d induced a significant increase in mEPSC amplitude, suggesting that dentate granule cells show robust synaptic up-scaling. The combination of denervation and TTX had no additive effect on the mean mEPSC amplitude (Figure 3; n = 5 cultures per group, 3–4 neurons recorded per culture).

Bottom Line: Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength.To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin.By using computational modeling and local electrical stimulations in Strontium (Sr(2+))-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3-4 days post lesion.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Frankfurt, Germany. a.vlachos@med.uni-frankfurt.de

ABSTRACT
Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥ 3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr(2+))-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3-4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro.

Show MeSH
Related in: MedlinePlus