Limits...
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

Developmental changes in sIPSC amplitude and frequency. (A) Representative examples of sIPSCs recordings for different age groups. (B) Group data for average resting input resistance in the different age groups. (C) Average sIPSC frequency for all age groups. (D) Average sIPSC amplitude for all age groups. For (B–D): black bar: P14; dark gray bar: P19; light gray bar: P21; lightest gray bar: P27. (E) Cumulative distribution of sIPSC amplitudes for the different age groups. (F) Cumulative distribution of sIPSC frequencies for the different age groups. For (E,F): black: P14; dark gray: P19; light gray: P21; lightest gray: P27. Data are presented as mean ± SEM, statistical significance is indicated by *** for P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928593&req=5

Figure 10: Developmental changes in sIPSC amplitude and frequency. (A) Representative examples of sIPSCs recordings for different age groups. (B) Group data for average resting input resistance in the different age groups. (C) Average sIPSC frequency for all age groups. (D) Average sIPSC amplitude for all age groups. For (B–D): black bar: P14; dark gray bar: P19; light gray bar: P21; lightest gray bar: P27. (E) Cumulative distribution of sIPSC amplitudes for the different age groups. (F) Cumulative distribution of sIPSC frequencies for the different age groups. For (E,F): black: P14; dark gray: P19; light gray: P21; lightest gray: P27. Data are presented as mean ± SEM, statistical significance is indicated by *** for P < 0.001.

Mentions: The maturation of the GABAergic system is critical for the onset of the critical period for visual cortical plasticity (Fagiolini and Hensch, 2000). Developmental changes of inhibitory synaptic transmission parallel the maturation of the endocannabinoids system. The restriction of pyramidal neurons capacity for CB-dependent inhibitory plasticity to the time immediately following eye opening suggests that this form of plasticity may be sensitive to visual experience. We investigated this directly by determining first how sIPSC properties may change during the developmental window under study and then by assessing the role of the time of eye opening on the capacity for CB-dependent inhibitory plasticity. In L4, sIPSC frequency increased significantly from P14 to P19 and then remained stable (P14, 1.47 ± 0.25 Hz, n = 13; P19, 2.51 ± 0.20 Hz, n = 13, P < 0.001; P21, 2.62 ± 0.13 Hz, n = 13, P < 0.001; P27, 2.93 ± 0.33 Hz, n = 13, one-way ANOVA with post hoc Tukey–Kramer test for multiple comparisons: P < 0.001; K–S test on distributions: P14–P19: P < 0.001; P19–P21: P < 0.002; P21–P27: P = 0.33; Figures 10A,C,F). Differently, the average sIPSC amplitude did not change significantly from P14 to P27 (P14, 28.3 ± 4.3 pA, n = 13; P19, 35.5 ± 2.6 pA, n= 13; P21, 36.0 ± 5.1 pA, n = 13; P27, 35.0 ± 2.4 pA, n = 13; one-way ANOVA with post hoc Tukey–Kramer test for multiple comparisons: P = 0.4); while the distribution of sIPSC amplitudes showed significant differences after P19, at the transition from the pre-critical to the critical period (K–S test on distributions: P14–P19: P = 0.08; P19–P21: P < 0.001; P21–P27: P < 0.001; Figures 10B,D,F). Thus, GABAergic sIPSCs in L4 of V1 progressively increase in frequency during development and reach a steady-state at P19, when CB-dependent potentiation of inhibition is still effectively induced and before the onset of the critical period for visual cortical plasticity. The amplitude of sIPSCs increased after the onset of the critical period, consistent with previous findings that inhibitory synapses maturation in mice V1 extends beyond the first three postnatal weeks (Morales et al., 2002). Together this data suggest that the capacity for CB-dependent inhibitory plasticity in L4 is not occluded by the maturation of GABAergic synaptic transmission. Instead, the process of maturation and capacity for CB-dependent potentiation of inhibition are parallel processes regulating inhibitory synaptic drive onto L4 pyramidal neurons during postnatal development.


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

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

Developmental changes in sIPSC amplitude and frequency. (A) Representative examples of sIPSCs recordings for different age groups. (B) Group data for average resting input resistance in the different age groups. (C) Average sIPSC frequency for all age groups. (D) Average sIPSC amplitude for all age groups. For (B–D): black bar: P14; dark gray bar: P19; light gray bar: P21; lightest gray bar: P27. (E) Cumulative distribution of sIPSC amplitudes for the different age groups. (F) Cumulative distribution of sIPSC frequencies for the different age groups. For (E,F): black: P14; dark gray: P19; light gray: P21; lightest gray: P27. Data are presented as mean ± SEM, statistical significance is indicated by *** for P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Developmental changes in sIPSC amplitude and frequency. (A) Representative examples of sIPSCs recordings for different age groups. (B) Group data for average resting input resistance in the different age groups. (C) Average sIPSC frequency for all age groups. (D) Average sIPSC amplitude for all age groups. For (B–D): black bar: P14; dark gray bar: P19; light gray bar: P21; lightest gray bar: P27. (E) Cumulative distribution of sIPSC amplitudes for the different age groups. (F) Cumulative distribution of sIPSC frequencies for the different age groups. For (E,F): black: P14; dark gray: P19; light gray: P21; lightest gray: P27. Data are presented as mean ± SEM, statistical significance is indicated by *** for P < 0.001.
Mentions: The maturation of the GABAergic system is critical for the onset of the critical period for visual cortical plasticity (Fagiolini and Hensch, 2000). Developmental changes of inhibitory synaptic transmission parallel the maturation of the endocannabinoids system. The restriction of pyramidal neurons capacity for CB-dependent inhibitory plasticity to the time immediately following eye opening suggests that this form of plasticity may be sensitive to visual experience. We investigated this directly by determining first how sIPSC properties may change during the developmental window under study and then by assessing the role of the time of eye opening on the capacity for CB-dependent inhibitory plasticity. In L4, sIPSC frequency increased significantly from P14 to P19 and then remained stable (P14, 1.47 ± 0.25 Hz, n = 13; P19, 2.51 ± 0.20 Hz, n = 13, P < 0.001; P21, 2.62 ± 0.13 Hz, n = 13, P < 0.001; P27, 2.93 ± 0.33 Hz, n = 13, one-way ANOVA with post hoc Tukey–Kramer test for multiple comparisons: P < 0.001; K–S test on distributions: P14–P19: P < 0.001; P19–P21: P < 0.002; P21–P27: P = 0.33; Figures 10A,C,F). Differently, the average sIPSC amplitude did not change significantly from P14 to P27 (P14, 28.3 ± 4.3 pA, n = 13; P19, 35.5 ± 2.6 pA, n= 13; P21, 36.0 ± 5.1 pA, n = 13; P27, 35.0 ± 2.4 pA, n = 13; one-way ANOVA with post hoc Tukey–Kramer test for multiple comparisons: P = 0.4); while the distribution of sIPSC amplitudes showed significant differences after P19, at the transition from the pre-critical to the critical period (K–S test on distributions: P14–P19: P = 0.08; P19–P21: P < 0.001; P21–P27: P < 0.001; Figures 10B,D,F). Thus, GABAergic sIPSCs in L4 of V1 progressively increase in frequency during development and reach a steady-state at P19, when CB-dependent potentiation of inhibition is still effectively induced and before the onset of the critical period for visual cortical plasticity. The amplitude of sIPSCs increased after the onset of the critical period, consistent with previous findings that inhibitory synapses maturation in mice V1 extends beyond the first three postnatal weeks (Morales et al., 2002). Together this data suggest that the capacity for CB-dependent inhibitory plasticity in L4 is not occluded by the maturation of GABAergic synaptic transmission. Instead, the process of maturation and capacity for CB-dependent potentiation of inhibition are parallel processes regulating inhibitory synaptic drive onto L4 pyramidal neurons during postnatal development.

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