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Synaptic plasticity at basal and apical dendrites of hippocampal neurons engage unique intracellular cascades and matrix metalloproteases subtypes

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Wojtowicz T., Brzdak P., Wojcicka O., Mozrzymas J. W.

Acta Neurobiologiae Experimentalis

2017

tom 77

nr Suppl.1

Cognitive processes such as learning and memory require functional modifications within neural circuits which involve reorganization of existing synaptic connections and modulation of its strength. In addition, neurons can significantly enhance information storage capacity by scaling dendritic and somatic excitability (e.g. EPSP-to-spike potentiation). Proteolysis of extracellular matrix constituents and membrane proteins by matrix metalloproteases (MMP) has recently emerged as a key element in these processes. We identified NMDARs as a target for MMP-3 but not MMP-2/9 immediately following LTP induction. We next applied confocal imaging for nuclear cFos protein in brain slices fixed immediately following electrophysiology studies and Ca2+ imaging for somatodendritic NMDAR-mediated Ca2+ waves. We concluded that long-term hippocampal E-S potentiation limited to stratum radiatum inputs required MMP-3 activity in a narrow time window following enhanced neuronal activity that promotes NMDAR-mediated postsynaptic Ca2+ entry and activation of downstream signaling cascades leading to immediate early genes transcription. Most recently we discovered that in striking contrast to apical dendrites, synaptic plasticity induced at basal dendrites was insensitive to a wide range of broad and subtype specific MMP inhibitors. Thus, stratum radiatum synapses required MMP-3, alpha 5-integrins or protease-activated receptor 1 (PAR-1) and PKC kinase activity for modulation of NMDARs function, unlike stratum oriens synapses. FINANCIAL SUPPORT: National Science Center grant no. SONATA/2014/13/D/NZ4/03045.

Role of dopamine D1\D5 receptors in modulating synaptic plasticity at basal and apical dendritic trees of pyramidal neurons in mouse hippocampus

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Wojcicka O., Mozrzymas J. W., Wojtowicz T.

Acta Neurobiologiae Experimentalis

2017

tom 77

nr Suppl.1

INTRODUCTION: Deciphering cellular mechanisms of neuronal circuits plasticity remains of key importance in understanding learning and memory. In the hippocampus, CA1 pyramidal neurons receive different amount of excitatory and modulatory dopaminergic inputs to basal and apical dendritic trees. This layer‑specific differential inputs may play a key role in encoding the respective memory traces. However the locus‑specific mechanism of synaptic plasticity remains poorly understood. AIM(S): The aim of the study was to identify to what extent dopamine receptors could regulate AMPARs and NMDARs function in long-term synaptic plasticity within basal and apical dendrites of pyramidal neurons. METHOD(S): We used combination of electrophysiological recordings (fEPSPs) and pharmacological treatment in acute hippocampal slices of adult P45-60 C57BL/6 male mice. RESULTS: High frequency stimulation (HFS, 4×100 Hz every 10 s) of afferent fibers within basal dendrites (stratum oriens, SO) led to significantly larger long‑term potentiation (LTP) of AMPARs-mediated fEPSPs (LTPAMPA) compared to apical dendrites (stratum radiatum, SR). When slices were incubated with dopamine D1/D5 receptors agonist (SKF‑38393 hydrochloride), LTPAMPA was significantly upregulated at SO but not SR synapses. However, in both projections bath applied NMDARs-antagonist (APV) completely abolished LTPAMPA indicating that NMDAR are indispensable in both SR and SO. We next pharmacologically isolated NMDAR‑mediated synaptic field‑potentials and found that D1/D5Rs agonist potentiated these signals in SO but not SR. We next found that priming of D1/D5Rs with its agonist occluded further potentiation of NMDAR function upon HFS. Moreover, application of D1/D5Rs antagonist (SCH23390) prevented gain in NMDAR function at SO, an effect never observed at SR synapses. CONCLUSIONS: Synaptic NMDARs located at basal and apical dendritic trees are differentially modulated by D1/ D5Rs. Dopamine-mediated modulation of NMDARs function could locus‑specific gain in AMPARs function at SO. FINANCIAL SUPPORT: National Science Center SONATA/2014/13/D/NZ4/03045.

Ograniczanie wyników

2 Acta Neurobiologiae Experimentalis

2 Mozrzymas J. W.

2 Wojcicka O.

2 Wojtowicz T.

1 Brzdak P.

2 2017

Wyniki wyszukiwania

Synaptic plasticity at basal and apical dendrites of hippocampal neurons engage unique intracellular cascades and matrix metalloproteases subtypes

Role of dopamine D1\D5 receptors in modulating synaptic plasticity at basal and apical dendritic trees of pyramidal neurons in mouse hippocampus