Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice
- Northwestern University, United States
Figures
Figure 1 with 2 supplements
Sex differences in CbN synaptic currents and sex-specific responses to the Gabrb3 m-/p+ mutation.
(A) 100-Hz trains of synaptic currents evoked in CbN cells from male and female wild-type mice, normalized to the first peak. Dotted line, baseline holding current. (B) Mean amplitudes of phasic …
Figure 1—figure supplement 1
Sex differences in tonic current and IPSC decay kinetics in C57BL/6 mice.
(A) Phasic current, as a percentage of initial IPSC amplitude, over 20 stimuli for C57BL/6 males (n=16) and females (n=16). The curves do not differ between males and females (p=0.9). (B) Tonic …
Figure 1—figure supplement 2
Tonic synaptic current, likely mediated by mGluR1/5, may be modulated by environmental conditions such as chronic stress.
Tonic current, as a percentage of initial IPSC amplitude, for 20 stimuli at 100 Hz for Gabrb3 +/+ male mice before (control) and during construction (construction), and C57BL/6 control male mice. …
Figure 2
Group I mGluRs account for differences in synaptic currents and responses to the Gabrb3 m-/p+ mutation.
(A) Synaptic currents in the presence of CPCCOEt evoked in CbN cells from male and female wild-type mice. Dotted line, baseline holding current. (B) Mean amplitudes of phasic (upper panel) and tonic …
Figure 3
Differences in mGluR1/5-dependent currents depend on glutamate access to receptors rather than receptor expression.
(A) Increase in holding current in a +/+ male mouse by TBOA reversal by group I mGluR antagonists. (B) Increase in holding current by TBOA reversal by TTX. Top: sample traces from a C57BL/6 male …
Figure 4
Group I mGluR-dependent and -independent effects of TBOA on evoked EPSCs.
(A) Sample traces from a CbN cell from a m-/p+ male of EPSCs elicited by 100 Hz stimulus trains, in control, TBOA, and TBOA + mGluR1/5 antagonist(s), normalized to the peak of the first EPSC. (B) …
Figure 5
Sex differences in spontaneous firing rates and evoked rebound firing, and sex-specific responses to the Gabrb3 m-/p+ mutation.
(A) Sample traces of spontaneous action potentials in CbN cells. (B) Action potential half-width vs. spontaneous firing rate for all cells from all groups. Open symbols, individual cells; closed …
Figure 6 with 3 supplements
Performance on the accelerating rotarod varies with sex and Gabrb3 and depends on GABAAR β3 expression only in Purkinje cells.
(A) Latency to fall vs. training day for Gabrb3 P22 males (left) and females (right). (B) Change in latency, calculated as the difference between the Day-1 fall latency and mean Day 5–7 fall for all …
Figure 6—figure supplement 1
Mouse weight does not account for differences in motor learning.
Weight of Gabrb3 mice (closed symbols) and Purkinje-specific Gabrb3 mice (open symbols) on or immediately after Day 7 of rotarod testing. For Gabrb3 mice, females were lighter than males (+/+ males …
Figure 6—figure supplement 2
Differences in performance on rotarod change over development.
(Top: ) Average latency to fall on Day 1 for all four age groups for males (left) and females (right). Only m-/p+ females showed variable day 1 latencies throughout development. (Bottom: ) Average Δ …
Figure 6—figure supplement 3
Selection of rotarod protocols that permit an increase in fall latency over training for transgenic mice on a 129S background.
(A) Change latency to fall on the accelerating rotarod for Purkinje-specific Gabrb3 mice, age P22, subjected to 2 daily trials with the rod accelerating to 30 rpm over 4 min. None of the four groups …
Figure 7
Differences in CbN cell tonic current depend on GABAAR β3 expression only in Purkinje cells.
(A) 100-Hz trains of synaptic currents evoked as in Figure 1 in CbN cells from Purkinje-specific Gabrb3 +/+ and m-/p+ male mice, normalized to the first peak. Dotted line, baseline holding current. …
Figure 8
Diagram of sex differences in mGluR1/5 and compensatory changes in males with loss of GABAAR β3.
(Top:) Expected relative levels of GABAAR β3 expression (red asterisks) in the cerebellar cortex, and mGluR1/5-dependent current amplitude (blue arrows) in large CbN cells. For simplicity, only …
