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Ovarian cycle-linked plasticity of δ-GABAA receptor subunits in hippocampal interneurons affects γ oscillations in vivo.

Barth AM, Ferando I, Mody I - Front Cell Neurosci (2014)

Bottom Line: Here we show δ-GABAARs changes during the mouse ovarian cycle in hippocampal cell types, with enhanced expression during diestrus in principal cells and specific INs.Such recurring changes in γ magnitude were not observed in non-cycling wild-type (WT) females, cycling females lacking δ-GABAARs only on PV-INs (PV-Gabrd (-/-)), and in male mice during a time course equivalent to the ovarian cycle.Our findings may explain the impaired memory and cognitive performance experienced by women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.

ABSTRACT
GABAA receptors containing δ subunits (δ-GABAARs) are GABA-gated ion channels with extra- and perisynaptic localization, strong sensitivity to neurosteroids (NS), and a high degree of plasticity. In selective brain regions they are expressed on specific principal cells and interneurons (INs), and generate a tonic conductance that controls neuronal excitability and oscillations. Plasticity of δ-GABAARs in principal cells has been described during states of altered NS synthesis including acute stress, puberty, ovarian cycle, pregnancy and the postpartum period, with direct consequences on neuronal excitability and network dynamics. The defining network events implicated in cognitive function, memory formation and encoding are γ oscillations (30-120 Hz), a well-timed loop of excitation and inhibition between principal cells and PV-expressing INs (PV + INs). The δ-GABAARs of INs can modify γ oscillations, and a lower expression of δ-GABAARs on INs during pregnancy alters γ frequency recorded in vitro. The ovarian cycle is another physiological event with large fluctuations in NS levels and δ-GABAARs. Stages of the cycle are paralleled by swings in memory performance, cognitive function, and mood in both humans and rodents. Here we show δ-GABAARs changes during the mouse ovarian cycle in hippocampal cell types, with enhanced expression during diestrus in principal cells and specific INs. The plasticity of δ-GABAARs on PV-INs decreases the magnitude of γ oscillations continuously recorded in area CA1 throughout several days in vivo during diestrus and increases it during estrus. Such recurring changes in γ magnitude were not observed in non-cycling wild-type (WT) females, cycling females lacking δ-GABAARs only on PV-INs (PV-Gabrd (-/-)), and in male mice during a time course equivalent to the ovarian cycle. Our findings may explain the impaired memory and cognitive performance experienced by women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD).

No MeSH data available.


Related in: MedlinePlus

Fluctuations in γ oscillation amplitudes recorded during REM sleep are absent in males and non-cycling WT females. (A)Left: diagram showing normalized γ amplitudes during REM sleep on consecutive days in a WT male mouse. Right: distribution of γ amplitudes (binned at 2 μV) in all REM phases recorded on two separate measurements taken 3 days apart. The 2 days are indicated on the left with red and blue arrows. Colored numbers indicate mean ± SEM of the corresponding γ amplitude histograms. (B) Summary data showing the absolute values of the differences between the normalized γ amplitudes during REM sleep in different groups of mice. In the cycling WT females the difference was calculated between days of diestrus and estrus. In WT males and non-cycling females the differences in γ amplitudes were determined at 3-day intervals that approximated the time difference between the estrus and diestrus of cycling female mice. Asterisks indicate significant difference from all other groups in a Tukey’s multiple comparison test following a one-way ANOVA.
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Figure 3: Fluctuations in γ oscillation amplitudes recorded during REM sleep are absent in males and non-cycling WT females. (A)Left: diagram showing normalized γ amplitudes during REM sleep on consecutive days in a WT male mouse. Right: distribution of γ amplitudes (binned at 2 μV) in all REM phases recorded on two separate measurements taken 3 days apart. The 2 days are indicated on the left with red and blue arrows. Colored numbers indicate mean ± SEM of the corresponding γ amplitude histograms. (B) Summary data showing the absolute values of the differences between the normalized γ amplitudes during REM sleep in different groups of mice. In the cycling WT females the difference was calculated between days of diestrus and estrus. In WT males and non-cycling females the differences in γ amplitudes were determined at 3-day intervals that approximated the time difference between the estrus and diestrus of cycling female mice. Asterisks indicate significant difference from all other groups in a Tukey’s multiple comparison test following a one-way ANOVA.

Mentions: The definition of REM sleep was further narrowed by accepting only zero activity + low δ segments longer than 20 s that were adjacent to a segment characterized by high δ + zero activity (putative NREM sleep) phase. The detected REM segments were filtered in the 𝜃 (5–12 Hz) and high γ (63–120 Hz) range and 𝜃 phases and γ magnitudes were calculated using Hilbert transforms (Figure 2C). 𝜃 phase coupled γ amplitudes were determined by calculating the difference between the min and max values of the 𝜃 phase triggered average γ magnitude. On Figures 2, 3, and 5 the γ amplitudes were normalized to the mean values across all days and then plotted as a function of days. For male and non-cycling female mice the differences in γ amplitudes were determined at 3 day intervals that approximated the time difference between the estrus and diestrus phases of cycling female mice.


Ovarian cycle-linked plasticity of δ-GABAA receptor subunits in hippocampal interneurons affects γ oscillations in vivo.

Barth AM, Ferando I, Mody I - Front Cell Neurosci (2014)

Fluctuations in γ oscillation amplitudes recorded during REM sleep are absent in males and non-cycling WT females. (A)Left: diagram showing normalized γ amplitudes during REM sleep on consecutive days in a WT male mouse. Right: distribution of γ amplitudes (binned at 2 μV) in all REM phases recorded on two separate measurements taken 3 days apart. The 2 days are indicated on the left with red and blue arrows. Colored numbers indicate mean ± SEM of the corresponding γ amplitude histograms. (B) Summary data showing the absolute values of the differences between the normalized γ amplitudes during REM sleep in different groups of mice. In the cycling WT females the difference was calculated between days of diestrus and estrus. In WT males and non-cycling females the differences in γ amplitudes were determined at 3-day intervals that approximated the time difference between the estrus and diestrus of cycling female mice. Asterisks indicate significant difference from all other groups in a Tukey’s multiple comparison test following a one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128222&req=5

Figure 3: Fluctuations in γ oscillation amplitudes recorded during REM sleep are absent in males and non-cycling WT females. (A)Left: diagram showing normalized γ amplitudes during REM sleep on consecutive days in a WT male mouse. Right: distribution of γ amplitudes (binned at 2 μV) in all REM phases recorded on two separate measurements taken 3 days apart. The 2 days are indicated on the left with red and blue arrows. Colored numbers indicate mean ± SEM of the corresponding γ amplitude histograms. (B) Summary data showing the absolute values of the differences between the normalized γ amplitudes during REM sleep in different groups of mice. In the cycling WT females the difference was calculated between days of diestrus and estrus. In WT males and non-cycling females the differences in γ amplitudes were determined at 3-day intervals that approximated the time difference between the estrus and diestrus of cycling female mice. Asterisks indicate significant difference from all other groups in a Tukey’s multiple comparison test following a one-way ANOVA.
Mentions: The definition of REM sleep was further narrowed by accepting only zero activity + low δ segments longer than 20 s that were adjacent to a segment characterized by high δ + zero activity (putative NREM sleep) phase. The detected REM segments were filtered in the 𝜃 (5–12 Hz) and high γ (63–120 Hz) range and 𝜃 phases and γ magnitudes were calculated using Hilbert transforms (Figure 2C). 𝜃 phase coupled γ amplitudes were determined by calculating the difference between the min and max values of the 𝜃 phase triggered average γ magnitude. On Figures 2, 3, and 5 the γ amplitudes were normalized to the mean values across all days and then plotted as a function of days. For male and non-cycling female mice the differences in γ amplitudes were determined at 3 day intervals that approximated the time difference between the estrus and diestrus phases of cycling female mice.

Bottom Line: Here we show δ-GABAARs changes during the mouse ovarian cycle in hippocampal cell types, with enhanced expression during diestrus in principal cells and specific INs.Such recurring changes in γ magnitude were not observed in non-cycling wild-type (WT) females, cycling females lacking δ-GABAARs only on PV-INs (PV-Gabrd (-/-)), and in male mice during a time course equivalent to the ovarian cycle.Our findings may explain the impaired memory and cognitive performance experienced by women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.

ABSTRACT
GABAA receptors containing δ subunits (δ-GABAARs) are GABA-gated ion channels with extra- and perisynaptic localization, strong sensitivity to neurosteroids (NS), and a high degree of plasticity. In selective brain regions they are expressed on specific principal cells and interneurons (INs), and generate a tonic conductance that controls neuronal excitability and oscillations. Plasticity of δ-GABAARs in principal cells has been described during states of altered NS synthesis including acute stress, puberty, ovarian cycle, pregnancy and the postpartum period, with direct consequences on neuronal excitability and network dynamics. The defining network events implicated in cognitive function, memory formation and encoding are γ oscillations (30-120 Hz), a well-timed loop of excitation and inhibition between principal cells and PV-expressing INs (PV + INs). The δ-GABAARs of INs can modify γ oscillations, and a lower expression of δ-GABAARs on INs during pregnancy alters γ frequency recorded in vitro. The ovarian cycle is another physiological event with large fluctuations in NS levels and δ-GABAARs. Stages of the cycle are paralleled by swings in memory performance, cognitive function, and mood in both humans and rodents. Here we show δ-GABAARs changes during the mouse ovarian cycle in hippocampal cell types, with enhanced expression during diestrus in principal cells and specific INs. The plasticity of δ-GABAARs on PV-INs decreases the magnitude of γ oscillations continuously recorded in area CA1 throughout several days in vivo during diestrus and increases it during estrus. Such recurring changes in γ magnitude were not observed in non-cycling wild-type (WT) females, cycling females lacking δ-GABAARs only on PV-INs (PV-Gabrd (-/-)), and in male mice during a time course equivalent to the ovarian cycle. Our findings may explain the impaired memory and cognitive performance experienced by women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD).

No MeSH data available.


Related in: MedlinePlus