Bilaterality index in mice with or without crossing nerve transfer.

<p>The bilaterality index in mice with crossing nerve transfer surgery using three different methods is significantly greater than that in naïve mice (P<0.0001, respectively). The bilaterality index is not significantly different between mice operated in an end-to-end fashion, with or without sequential nerve cut. However, the index in mice operated in an end-to-side fashion was significantly larger than that in mice operated in an end-to-end fashion with (P<0.002) or without sequential nerve cut (P<0.007). Numbers in the parentheses show the numbers of mice.</p

Bilateral cortical representation induced by direct cortical stimulation.

<p>(A) Cortical responses elicited by left forepaw stimulation before (a), within 20 min (b) and more than 40 min (c) after cessation of direct stimulation applied to the ipsilateral left S1 paired with left forepaw stimulation in the same mouse. These experiments were performed in naïve mice. The black dot in (a–c) shows the direct cortical stimulation site. (B) Amplitudes of cortical responses elicited by left forepaw stimulation in the ipsilateral left S1 (red) and contralateral right S1 (blue).</p

Crossing nerve transfer in cPcdhα knockout mice.

<p>(A) Cortical responses elicited by transcranial stimulation of the left S1 in control cPcdhα +/+ (a) and cPcdhα −/− mice (b). Responses in a cortex-restricted GluN1 +/− mouse are also shown for comparison (c). (B) Bilaterality index of cortical responses elicited by transcranial stimulation of the left S1 in cPcdhα +/+, cPcdhα −/−, and cortex-restricted GluN1 +/− mice. (C) Cortical responses elicited by left forepaw stimulation at 8 weeks after crossing nerve transfer in cPcdhα +/+ (a) and cPcdhα −/− mice (b). (D) Bilaterality index after crossing nerve transfer in cPcdhα +/+ and cPcdhα −/− mice.</p

Crossing nerve transfer surgery.

<p>The cut ends of the left median (MN) and ulnar nerves (UN) were connected to the right brachial plexus (BP) via a sciatic nerve graft at 8 weeks of age. The left radial (RN) and musculocutaneous nerves (McN) were cut at the same time, or at 15 weeks of age (sequential nerve cut). Imaging was performed at 16 weeks of age.</p

Crossing nerve transfer in cortex-restricted heterozygous GluN1 knockout mice.

<p>(A) Cortical responses elicited by left forepaw stimulation after crossing nerve transfer in control GluN1 +/+ (a) and cortex-restricted GluN1 +/− mice (b). (B) Amplitudes of cortical responses recorded in the ipsilateral left S1 after crossing nerve transfer. Control GluN1 +/+ mice expressed Cre alone, LoxP alone, or neither, and cortex-restricted GluN1 +/− mice expressed both Cre and LoxP. (C) Amplitudes of cortical responses recorded in the contralateral right S1 after crossing nerve transfer. (D) Bilaterality index after crossing nerve transfer in control GluN1 +/+ and cortex-restricted GluN1 +/− mice. The index in naïve mice is also shown for comparison.</p

Cortical responses before and after crossing nerve transfer.

<p>(A) Cortical responses elicited by vibratory stimulation applied to the left forepaw in a naïve mouse. In the left diagram (a), peripheral nerves are shown on the back of a mouse to avoid left-right confusion. The middle panel (b) shows the original fluorescence image. In the right panel (c), neural activity is apparent in the contralateral right S1, while the ipsilateral left S1 is only weakly activated. (B) Cortical responses after crossing nerve transfer. The diagram (a) and cortical responses elicited by vibratory stimulation applied to the left forepaw at 4 weeks (b), 8 weeks (c and d), 8 months (e) and 12 months (f) after crossing nerve transfer. The cortical responses shown in (c) were almost completely lost after the nerve graft was cut in the same mouse (d).</p

Activity-dependent mechanisms underlying bilateral cortical representation.

<p>(A) Neural circuits prior to crossing nerve transfer. Cortico-cortical inputs from the left S1 to the right S1 are not necessarily synchronous to other non-thalamic inputs to the right S1, because sensory inputs from both forepaws are not necessarily synchronous. In contrast, thalamic inputs to the right S1 are synchronous to other non-thalamic inputs to the right S1. (B) Neural circuits after crossing nerve transfer. Cortico-cortical inputs from the left S1 to the right S1 are now synchronous to other non-thalamic inputs to the right S1, so that the cortico-cortical inputs can be synchronized with postsynaptic activities in the right S1. Cortico-cortical synapses from the left S1 to the right S1 are potentiated according to the Hebbian rule.</p