Sustained Structural Change of GABAA Receptor-Associated Protein Underlies Long-Term Potentiation at Inhibitory Synapses on a Cerebellar Purkinje Neuron

Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed a specific deficit in contextual fear memory, both short-term and long-term after conditioning, whereas auditory fear memory and anxiety-related behavior were normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory recall.

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High-Frequency Stimulation Together with Adrenoceptor Activation Facilitates the Maintenance of Long-Term Potentiation at Visual Cortical Inhibitory Synapses

Cerebral Cortex ◽

10.1093/cercor/bhj065 ◽

2005 ◽

Vol 16 (9) ◽

pp. 1239-1248 ◽

Cited By ~ 8

Author(s):

Kazumasa Yamada ◽

Tsuyoshi Inagaki ◽

Rie Funahashi ◽

Yumiko Yoshimura ◽

Yukio Komatsu

Keyword(s):

High Frequency ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

High Frequency Stimulation ◽

Term Potentiation ◽

Frequency Stimulation ◽

Visual Cortical

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Learning-related long-term potentiation of inhibitory synapses in the cerebellar cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0706342105 ◽

2008 ◽

Vol 105 (2) ◽

pp. 769-774 ◽

Cited By ~ 44

Author(s):

B. Scelfo ◽

B. Sacchetti ◽

P. Strata

Keyword(s):

Cerebellar Cortex ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

Term Potentiation

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A physiological role for GABAA receptor desensitization – induction of long-term potentiation at inhibitory synapses

10.1101/2020.06.02.128900 ◽

2020 ◽

Cited By ~ 1

Author(s):

Martin Field ◽

Philip Thomas ◽

Trevor G Smart

Keyword(s):

Physiological Role ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

Structural Basis ◽

Inhibitory Neurotransmission ◽

Term Potentiation ◽

Physiological Relevance ◽

Kinetic Effects ◽

Physiological Impact

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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