SYNAPTIC PLASTICITY IN THE ISCHAEMIC BRAIN Liang Hua-wei
SYNAPTIC PLASTICITY IN THE ISCHAEMIC BRAIN Liang Hua-wei
Synaptic Plasticity Morphological changes ·Functional changes Long-term potentiation(LTP) Long-term depression (LTD)
Synaptic Plasticity ? • Morphological changes • Functional changes Long-term potentiation (LTP) Long-term depression (LTD)
Pathological Plasticity Induced by Energy Deprivation in Vitro ·Hippocampal neurons Under physiological conditions a4
Pathological Plasticity Induced by Energy Deprivation in Vitro • Hippocampal neurons Under physiological conditions
Under anoxic or ischaemic conditions Schaffer collaterals Focal application of NMDA Intracellular recordings CA Control Anoxic +60 min /aglycemie episode (2 min) 200p4
Under anoxic or ischaemic conditions
Characteristic of anoxic LTP in the Cal area Voltage and NMDA-receptor dependent An increase in [Ca2+]is required Both presynaptic and postsynaptic loci is involved Its expression mediated exclusively by NMDA receptors
Characteristic of anoxic LTP in the CA1 area • Voltage and NMDA-receptor dependent • An increase in [Ca2+]i is required • Both presynaptic and postsynaptic loci is involved • Its expression mediated exclusively by NMDA receptors
Characteristic of aglycaemic LTP in the CAl area Not pathway-specific Not prevented by preceding tetanic LTP Insensitive to NOS inhibitor An increase in [Ca2+]is not the main trigger
Characteristic of aglycaemic LTP in the CA1 area • Not pathway-specific • Not prevented by preceding tetanic LTP • Insensitive to NOS inhibitor • An increase in [Ca2+]i is not the main trigger
·Striatal neurons Cerebral ischaemia induces membrane depolarisation mediated by sodium and calcium ion inlux Synaptic LTP mediated by the NMDA receptor 3 min ischaemia 20 min 10 mV interruption 10 mV 10ms Ischaemia in vitro depolarises a striatal spiny neuron and induces postischaemic LTP
Ischaemia in vitro depolarises a striatal spiny neuron and induces postischaemic LTP • Striatal neurons
Ischaemia induces a membrane Ischaemia does not induce hyperpolarisation mediated by longterm changes in excitatory potassium ion efflux syaptic transmission 3 min ischaemia B 20 min interruption 10 mV 1min 10 mV Excitatory postsynaptic Excitatory postsynaptic potential 30 min 10 ms potential preischaemia postischaemia Ischaemia in vitro hyperpolarises a striatal interneuron and fails to induce postischaemic LTP
Ischaemia in vitro hyperpolarises a striatal interneuron and fails to induce postischaemic LTP
Characteristic of postischaemic LTP in spiny neurons Also occurs in synaptic pathways that are not active during ischaemia Blocked by inhibitors of MAP kinase Endogenous acetylcholine is required for physiological but not for pathological synaptic potentiation
Characteristic of postischaemic LTP in spiny neurons • Also occurs in synaptic pathways that are not active during ischaemia • Blocked by inhibitors of MAP kinase • Endogenous acetylcholine is required for physiological but not for pathological synaptic potentiation
Morphological changes induced by activity-dependent LTP and by ischaemic episodes Enlargements of the spine head Shortening of the spine neck Formation of perforated synapses Formation of new spines Postsynaptic densities in the CAl and the dentate gyrus were thicker,more irregular and loosely configured in postischaemic brains
Morphological changes induced by activity-dependent LTP and by ischaemic episodes • Enlargements of the spine head • Shortening of the spine neck • Formation of perforated synapses • Formation of new spines • Postsynaptic densities in the CA1 and the dentate gyrus were thicker, more irregular and loosely configured in postischaemic brains