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 (Sr2+)-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.
Highlights
Denervation-induced plasticity is a form of neuronal plasticity that is of particular interest in the context of neurological diseases
Associational fibers which arise from glutamatergic mossy cells in the hilus and which terminate in the inner molecular layer (IML) of the dentate gyrus are not injured by the lesion [8,9,12,13]
To assess the effects of entorhinal denervation on glutamatergic synaptic strength, miniature excitatory postsynaptic currents were recorded from control and denervated granule cells using whole-cell patch-clamp recordings at 3 h, 6 h, 12 h, 24 h, 48 h, 3–4 dpl, 7 dpl, 10 dpl and 14 dpl
Summary
Denervation-induced plasticity is a form of neuronal plasticity that is of particular interest in the context of neurological diseases. Since neurons are highly interconnected cells, the degeneration of a given neuronal population will inevitably result in the denervation of its target neurons If this denervation is sufficiently extensive, transneuronal changes of the denervated neurons may occur, ranging from spine loss and dendritic atrophy to cell death [1,2]. The loss of afferents, induces other plastic changes such as collateral sprouting of the remaining axons and reactive synaptogenesis [1,2]. These denervation-induced forms of neuronal plasticity compensate at least in part for the loss of afferent innervation and may play a pivotal role for the functional recovery of denervated neurons following denervation
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