, 2005) This phenomenon was reproduced in E18 5 control mice by

, 2005). This phenomenon was reproduced in E18.5 control mice by the combined application of the GABAA receptor blocker picrotoxin (PTX, 10–30 μM) and the glycine receptor blocker strychnine (Strych, 0.3–0.5 μM; n = 5) (Figure 6A: left, control; right, PTX plus Strych). These effects are seen as progressive changes in the phase values of ventral root bursts that are shifted from left-right

and flexor-extensor alternation (phase values around 0.5) to left-right and flexor-extensor synchrony (phase values around 0) (Figure 6A1). The circular plots summarize the normal left-right and flexor-extensor alternation (black squares) and their change into synchronization after total blockade of inhibition (red circles) in five independent experiments using control E18.5 embryos (Figure 6A2). A prominent LY2835219 difference in this pattern was seen in Vglut2-KO mice.

Here, during NMDA/5-HT/DA induced rhythmic activity, the combined application of the same doses of PTX and strychnine initially increased the frequency of the activity, then slowed it down and eventually led to the uncoupling selleck screening library of bursts in all roots (Figure 6B: left, control; right, PTX plus strychnine; n = 8, Figure 6B1). This effect is seen as an insignificant coupling between individual roots after blockade of inhibition (Figures 6B1 and 6B2, red circles), and it was observed in all the experiments carried out in Vglut2-KO mice (n = 8). Thus, blockade of inhibition in Vglut2-KO mice resulted in low amplitude and slow frequency oscillations Terminal deoxynucleotidyl transferase in MNs. In induced Vglut2-KO mice that otherwise had a locomotor phenotype similar to chronic Vglut2-KO mice, there was a change from alternation into synchronization after

total blockade of inhibition, similar to controls (n = 4; data not shown). The 10%–20% remaining Vglut2 protein seen in induced Vglut2-KO was apparently enough to coordinate synchronous activity. These experiments show that coordination of the drug-induced rhythmic activity observed in chronic Vglut2-KO mice is completely dependent on a GABAA/glycinergic inhibitory network. The experiments blocking inhibitory synaptic transmission suggest that rhythm and pattern generation in the Vglut2 knockout is produced by a network of inhibitory neurons. Well-known inhibitory neurons that provide rhythmic inhibition of MNs during normal locomotor activity are the RCs and the rIa-INs. We first assessed whether the rIa-IN pathway was present in E18.5 Vglut2-KO mice. We took advantage of the recent demonstration that, like cats, newborn mice display a strong Ia-mediated reciprocal inhibition between the knee extensor quadriceps and the knee flexor posterior biceps-semitendinosus (PBST) (Wang et al., 2008).

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