Post-ischaemic long-term synaptic potentiation in the striatum: a putative mechanism for cell type-specific vulnerability.
In the present in vitro study of rat brain, we report that transient oxygen and glucose deprivation (in vitro ischaemia) induced a post-ischaemic long-term synaptic potentiation (i-LTP) at corticostriatal synapses. We compared the physiological and pharmacological characteristics of this pathological form of synaptic plasticity with those of LTP induced by tetanic stimulation of corticostriatal fibres (t-LTP), which is thought to represent a cellular substrate of learning and memory. Activation of N-methyl-D-aspartate (NMDA) receptors was required for the induction of both forms of synaptic plasticity. The intraneuronal injection of the calcium chelator BAPTA [bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate] and inhibitors of the mitogen-activated protein kinase pathway blocked both forms of synaptic plasticity. However, while t-LTP showed input specificity, i-LTP occurred also at synaptic pathways inactive during the ischaemic period. In addition, scopolamine, a muscarinic receptor antagonist, prevented the induction of t-LTP but not of i-LTP, indicating that endogenous acetylcholine is required for physiological but not for pathological synaptic potentiation. Finally, we found that striatal cholinergic interneurones, which are resistant to in vivo ischaemia, do not express i-LTP while they express t-LTP. We suggest that i-LTP represents a pathological form of synaptic plasticity that may account for the cell type-specific vulnerability observed in striatal spiny neurones following ischaemia and energy deprivation.
Calabresi
Paolo
P
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Tor Vergata and IRCCS Fondazione Santa Lucia, Rome, Italy. calabre@uniroma2.it
Saulle
Emilia
E
Centonze
Diego
D
Pisani
Antonio
A
Marfia
Girolama A
GA
Bernardi
Giorgio
G
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D016923:Cell Death / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D002614:Chelating Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D007395:Interneurons / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017072:Neostriatum / Q000378:metabolism* / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D017470:Receptors, Glutamate; D008274:Magnesium; D000109:Acetylcholine