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Cannabinoid-dependent potentiation of inhibition at eye opening in mouse V1.

Garkun Y, Maffei A - Front Cell Neurosci (2014)

Bottom Line: More specifically, application of synthetic and endogenous CB receptors agonists led to a significant increase in the amplitude and frequency of both spontaneous inhibitory post-synaptic currents and miniature inhibitory post-synaptic currents.This form of inhibitory potentiation is activity-dependent, induced by repetitive bursting of pyramidal neurons and regulated by the time of eye opening.CB-dependent regulation of inhibitory drive may be a mechanism for the regulating L4 pyramidal neurons excitability and function at a time in which V1 transitions from being activated by spontaneous activity to being driven by visual inputs.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology and Behavior, The State University of New York-Stony Brook University Stony Brook, NY, USA.

ABSTRACT
Cannabinoid (CB) signaling is a well established regulator of synaptic transmission. Recent work demonstrated that CB release is necessary for the induction of inhibitory synaptic plasticity. In primary visual cortex (V1) CB receptors are present throughout life, though their level of expression is developmentally regulated. In the input layer of V1 (layer 4, L4) these receptors show low levels of expression and colocalize with GABAergic terminals suggesting that they may play an important role in regulating GABAergic transmission. Here we show that in the developmental window extending from eye opening to the onset of the critical period for visual cortical plasticity L4 inhibitory inputs onto pyramidal neurons are highly sensitive to activation of CB release. More specifically, application of synthetic and endogenous CB receptors agonists led to a significant increase in the amplitude and frequency of both spontaneous inhibitory post-synaptic currents and miniature inhibitory post-synaptic currents. This form of inhibitory potentiation is activity-dependent, induced by repetitive bursting of pyramidal neurons and regulated by the time of eye opening. CB-dependent regulation of inhibitory drive may be a mechanism for the regulating L4 pyramidal neurons excitability and function at a time in which V1 transitions from being activated by spontaneous activity to being driven by visual inputs.

No MeSH data available.


Related in: MedlinePlus

Binocular lid suture delays the window for CB-dependent potentiation of inhibition. (A) Example traces of sIPSCs recordings in Control and after application of WIN (WIN 55,212-2, 1 μM) in animal whose time of eye opening was delayed from P13 to P27 with binocular eyelid suture (2 eye LS). Recording were performed at P27 – a time in development in which sIPSCs from normally reared mice show no sensitivity to WIN. (B) Average sIPSCs traces for the conditions shown in (A). Black: 2 eye LS; gray: 2 eye LS + WIN. (C) Bar plot summarizing the effect of WIN 55,212-2 on average sIPSC amplitude and frequency in binocularly deprived mice. Black: 2 eye LS; white: 2 eye LS + WIN. Data are expressed relative to Control to show fold changes. (D) Cumulative distribution of sIPSC amplitudes for control (2 eye LS) and WIN application (2 eye LS + WIN) in binocularly deprived mice. (E) Cumulative distribution of sIPSC frequencies for control (2 eye LS, black) and WIN application (2 eye LS + WIN, gray) in binocularly deprived mice. Data are presented as mean ± SEM, statistical significance is indicated by * for P < 0.05.
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Figure 11: Binocular lid suture delays the window for CB-dependent potentiation of inhibition. (A) Example traces of sIPSCs recordings in Control and after application of WIN (WIN 55,212-2, 1 μM) in animal whose time of eye opening was delayed from P13 to P27 with binocular eyelid suture (2 eye LS). Recording were performed at P27 – a time in development in which sIPSCs from normally reared mice show no sensitivity to WIN. (B) Average sIPSCs traces for the conditions shown in (A). Black: 2 eye LS; gray: 2 eye LS + WIN. (C) Bar plot summarizing the effect of WIN 55,212-2 on average sIPSC amplitude and frequency in binocularly deprived mice. Black: 2 eye LS; white: 2 eye LS + WIN. Data are expressed relative to Control to show fold changes. (D) Cumulative distribution of sIPSC amplitudes for control (2 eye LS) and WIN application (2 eye LS + WIN) in binocularly deprived mice. (E) Cumulative distribution of sIPSC frequencies for control (2 eye LS, black) and WIN application (2 eye LS + WIN, gray) in binocularly deprived mice. Data are presented as mean ± SEM, statistical significance is indicated by * for P < 0.05.

Mentions: In contrast, bath application of WIN 55,212-2 (1 μM) significantly increased amplitude and frequency of sIPSC recorded from slices obtained from P27 binocularly deprived mice (amplitude: 116.1 ± 5.9%; K–S test on distributions: P < 0.001; p-t on average data: P < 0.01; frequency: 125.0 ± 8.4% of baseline; K–S test on distributions: P < 0.001; p-t on average data: P < 0.007; n= 15; Figure 11), while it did not affect sIPSC amplitude of the non-deprived littermates. These data demonstrate that the capacity of L4 pyramidal neurons to induce CB-dependent potentiation of inhibition is independent of the maturation of GABAergic synapses, but is regulated by the time of eye opening.


Cannabinoid-dependent potentiation of inhibition at eye opening in mouse V1.

Garkun Y, Maffei A - Front Cell Neurosci (2014)

Binocular lid suture delays the window for CB-dependent potentiation of inhibition. (A) Example traces of sIPSCs recordings in Control and after application of WIN (WIN 55,212-2, 1 μM) in animal whose time of eye opening was delayed from P13 to P27 with binocular eyelid suture (2 eye LS). Recording were performed at P27 – a time in development in which sIPSCs from normally reared mice show no sensitivity to WIN. (B) Average sIPSCs traces for the conditions shown in (A). Black: 2 eye LS; gray: 2 eye LS + WIN. (C) Bar plot summarizing the effect of WIN 55,212-2 on average sIPSC amplitude and frequency in binocularly deprived mice. Black: 2 eye LS; white: 2 eye LS + WIN. Data are expressed relative to Control to show fold changes. (D) Cumulative distribution of sIPSC amplitudes for control (2 eye LS) and WIN application (2 eye LS + WIN) in binocularly deprived mice. (E) Cumulative distribution of sIPSC frequencies for control (2 eye LS, black) and WIN application (2 eye LS + WIN, gray) in binocularly deprived mice. Data are presented as mean ± SEM, statistical significance is indicated by * for P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928593&req=5

Figure 11: Binocular lid suture delays the window for CB-dependent potentiation of inhibition. (A) Example traces of sIPSCs recordings in Control and after application of WIN (WIN 55,212-2, 1 μM) in animal whose time of eye opening was delayed from P13 to P27 with binocular eyelid suture (2 eye LS). Recording were performed at P27 – a time in development in which sIPSCs from normally reared mice show no sensitivity to WIN. (B) Average sIPSCs traces for the conditions shown in (A). Black: 2 eye LS; gray: 2 eye LS + WIN. (C) Bar plot summarizing the effect of WIN 55,212-2 on average sIPSC amplitude and frequency in binocularly deprived mice. Black: 2 eye LS; white: 2 eye LS + WIN. Data are expressed relative to Control to show fold changes. (D) Cumulative distribution of sIPSC amplitudes for control (2 eye LS) and WIN application (2 eye LS + WIN) in binocularly deprived mice. (E) Cumulative distribution of sIPSC frequencies for control (2 eye LS, black) and WIN application (2 eye LS + WIN, gray) in binocularly deprived mice. Data are presented as mean ± SEM, statistical significance is indicated by * for P < 0.05.
Mentions: In contrast, bath application of WIN 55,212-2 (1 μM) significantly increased amplitude and frequency of sIPSC recorded from slices obtained from P27 binocularly deprived mice (amplitude: 116.1 ± 5.9%; K–S test on distributions: P < 0.001; p-t on average data: P < 0.01; frequency: 125.0 ± 8.4% of baseline; K–S test on distributions: P < 0.001; p-t on average data: P < 0.007; n= 15; Figure 11), while it did not affect sIPSC amplitude of the non-deprived littermates. These data demonstrate that the capacity of L4 pyramidal neurons to induce CB-dependent potentiation of inhibition is independent of the maturation of GABAergic synapses, but is regulated by the time of eye opening.

Bottom Line: More specifically, application of synthetic and endogenous CB receptors agonists led to a significant increase in the amplitude and frequency of both spontaneous inhibitory post-synaptic currents and miniature inhibitory post-synaptic currents.This form of inhibitory potentiation is activity-dependent, induced by repetitive bursting of pyramidal neurons and regulated by the time of eye opening.CB-dependent regulation of inhibitory drive may be a mechanism for the regulating L4 pyramidal neurons excitability and function at a time in which V1 transitions from being activated by spontaneous activity to being driven by visual inputs.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology and Behavior, The State University of New York-Stony Brook University Stony Brook, NY, USA.

ABSTRACT
Cannabinoid (CB) signaling is a well established regulator of synaptic transmission. Recent work demonstrated that CB release is necessary for the induction of inhibitory synaptic plasticity. In primary visual cortex (V1) CB receptors are present throughout life, though their level of expression is developmentally regulated. In the input layer of V1 (layer 4, L4) these receptors show low levels of expression and colocalize with GABAergic terminals suggesting that they may play an important role in regulating GABAergic transmission. Here we show that in the developmental window extending from eye opening to the onset of the critical period for visual cortical plasticity L4 inhibitory inputs onto pyramidal neurons are highly sensitive to activation of CB release. More specifically, application of synthetic and endogenous CB receptors agonists led to a significant increase in the amplitude and frequency of both spontaneous inhibitory post-synaptic currents and miniature inhibitory post-synaptic currents. This form of inhibitory potentiation is activity-dependent, induced by repetitive bursting of pyramidal neurons and regulated by the time of eye opening. CB-dependent regulation of inhibitory drive may be a mechanism for the regulating L4 pyramidal neurons excitability and function at a time in which V1 transitions from being activated by spontaneous activity to being driven by visual inputs.

No MeSH data available.


Related in: MedlinePlus