The paper deals with singular first order Hamiltonian systems of the form \[ \Gamma_k\dot{z}_k(t)=J\nabla_{z_k} H\big(z(t)\big),\quad z_k(t) \in \Omega \subset \mathbb{R}^2,\ k=1,\dots,N, \] where $J\in\mathbb{R}^{2\times2}$ defines the standard symplectic structure in $\mathbb{R}^2$, and the Hamiltonian $H$ is of $N$-vortex type: \[ H(z_1,\dots,z_N) = -\frac1{2\pi} \sum_{j\neq k=1}^N \Gamma_j \Gamma_k \log|z_j-z_k| - F(z). \] This is defined on the configuration space $\{(z_1,\ldots,z_N)\in \Omega^{2N}:z_j\neq z_k\text{ for }j\neq k\}$ of $N$ different points in the domain $\Omega\subset\mathbb{R}^2$. The function $F:\Omega^N\to\mathbb{R}$ may have additional singularities near the boundary of $\Omega^N$. We prove the existence of a global continuum of periodic solutions $z(t)=(z_1(t),\dots,z_N(t))\in\Omega^N$ that emanates, after introducing a suitable singular limit scaling, from a relative equilibrium $Z(t)\in\mathbb{R}^{2N}$ of the $N$-vortex problem in the whole plane (where $F=0$). Examples for $Z$ include Thomson's vortex configurations, or equilateral triangle solutions. The domain $\Omega$ need not be simply connected. A special feature is that the associated action integral is not defined on an open subset of the space of $2\pi$-periodic $H^{1/2}$ functions, the natural form domain for first order Hamiltonian systems. This is a consequence of the singular character of the Hamiltonian. Our main tool in the proof is a degree for $S^1$-equivariant gradient maps that we adapt to this class of potential operators.
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