Integrin α3β1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron

AbstractGABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

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Brain is modulated by neuronal plasticity during postnatal development

The Journal of Physiological Sciences ◽

10.1186/s12576-021-00819-9 ◽

2021 ◽

Vol 71 (1) ◽

Author(s):

Masoumeh Kourosh-Arami ◽

Nasrin Hosseini ◽

Alireza Komaki

Keyword(s):

Activity Patterns ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

Neural Systems ◽

Neural Structure ◽

Term Potentiation ◽

Study Results ◽

Development Processes ◽

Adaptation Processes

AbstractNeuroplasticity is referred to the ability of the nervous system to change its structure or functions as a result of former stimuli. It is a plausible mechanism underlying a dynamic brain through adaptation processes of neural structure and activity patterns. Nevertheless, it is still unclear how the plastic neural systems achieve and maintain their equilibrium. Additionally, the alterations of balanced brain dynamics under different plasticity rules have not been explored either. Therefore, the present article primarily aims to review recent research studies regarding homosynaptic and heterosynaptic neuroplasticity characterized by the manipulation of excitatory and inhibitory synaptic inputs. Moreover, it attempts to understand different mechanisms related to the main forms of synaptic plasticity at the excitatory and inhibitory synapses during the brain development processes. Hence, this study comprised surveying those articles published since 1988 and available through PubMed, Google Scholar and science direct databases on a keyword-based search paradigm. All in all, the study results presented extensive and corroborative pieces of evidence for the main types of plasticity, including the long-term potentiation (LTP) and long-term depression (LTD) of the excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs).

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Presynaptic Activity and Ca2+ Entry Are Required for the Maintenance of NMDA Receptor–Independent LTP at Visual Cortical Excitatory Synapses

Journal of Neurophysiology ◽

10.1152/jn.00602.2003 ◽

2004 ◽

Vol 92 (2) ◽

pp. 1077-1087 ◽

Cited By ~ 13

Author(s):

Hong Nian Liu ◽

Tohru Kurotani ◽

Ming Ren ◽

Kazumasa Yamada ◽

Yumiko Yoshimura ◽

...

Keyword(s):

Nmda Receptor ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

Excitatory Synapses ◽

Test Stimulation ◽

Term Potentiation ◽

Pharmacological Blockade ◽

Visual Cortical ◽

P Type

We have shown that some neural activity is required for the maintenance of long-term potentiation (LTP) at visual cortical inhibitory synapses. We tested whether this was also the case in N-methyl-d-aspartate (NMDA) receptor–independent LTP of excitatory connections in layer 2/3 cells of developing rat visual cortex. This LTP occurred after 2-Hz stimulation was applied for 15 min and always persisted for several hours while test stimulation was continued at 0.1 Hz. When test stimulation was stopped for 1 h after LTP induction, only one-third of the LTP instances disappeared, but most did disappear under a pharmacological suppression of spontaneous firing, indicating that LTP maintenance requires either evoked or spontaneous activities. LTP was totally abolished by a temporary blockade of action potentials with lidocaine or the removal of extracellular Ca2+ after LTP induction, but it persisted under a voltage clamp of postsynaptic cells or after a temporary blockade of postsynaptic activity with the glutamate receptor antagonist kynurenate, suggesting that LTP maintenance requires presynaptic, but not postsynaptic, firing and Ca2+ entry. More than one-half of the LTP instances were abolished after a pharmacological blockade of P-type Ca2+ channels, whereas it persisted after either L-type or Ni2+-sensitive Ca2+ channel blockades. These results show that the maintenance of NMDA receptor–independent excitatory LTP requires presynaptic firing and Ca2+ channel activation as inhibitory LTP, although the necessary level of firing and Ca2+ entry seems lower for the former than the latter and the Ca2+ channel types involved are only partly the same.

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2-Deoxyglucose–Induced Long-Term Potentiation of Monosynaptic IPSPs in CA1 Hippocampal Neurons

Journal of Neurophysiology ◽

10.1152/jn.2000.83.2.879 ◽

2000 ◽

Vol 83 (2) ◽

pp. 879-887 ◽

Cited By ~ 1

Author(s):

Krešimir Krnjević ◽

Yong-Tao Zhao

Keyword(s):

Hippocampal Neurons ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

Current Clamp ◽

Glutamate Antagonists ◽

Postsynaptic Potentials ◽

Postsynaptic Currents ◽

Inhibitory Postsynaptic Potentials ◽

Term Potentiation

In previous experiments on excitatory synaptic transmission in CA1, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose (2-DG) consistently caused a marked and very sustained potentiation (2-DG LTP). To find out whether 2-DG has a similar effect on inhibitory synapses, we recorded pharmacologically isolated mononosynaptic inhibitory postsynaptic potentials (IPSPs; under current clamp) and inhibitory postsynaptic currents (IPSCs; under voltage clamp); 2-DG was applied both in the presence and the absence of antagonists of N-methyl-d-aspartate (NMDA). In spite of sharply varied results (some neurons showing large potentiation, lasting for >1 h, and many little or none), overall there was a significant and similar potentiation of IPSP conductance, both for the early (at ≈30 ms) and later (at ≈140 ms) components of IPSPs or IPSCs: by 35.1 ± 10.25% (mean ± SE; for n = 24, P = 0.0023) and 36.5 ± 16.3% (for n = 19, P = 0.038), respectively. The similar potentiation of the early and late IPSP points to a presynaptic mechanism of LTP. Overall, the LTP was statistically significant only when 2-DG was applied in the absence of glutamate antagonists. Tetanic stimulations (in presence or absence of glutamate antagonists) only depressed IPSPs (by half). In conclusion, although smaller and more variable, 2-DG–induced LTP of inhibitory synapses appears to be broadly similar to the 2-DG–induced LTP of excitatory postsynaptic potentials previously observed in CA1.

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