Anatomy of a songbird basal ganglia circuit essential for vocal learning and plasticity

Abstract

Vocal learning in songbirds requires an anatomically discrete and functionally dedicated circuit called the anterior forebrain pathway (AFP). The AFP is homologous to cortico-basal ganglia-thalamo-cortical loops in mammals. The basal ganglia portion of this pathway, Area X, shares many features characteristic of the mammalian striatum and pallidum, including cell types and connectivity. The AFP also deviates from mammalian basal ganglia circuits in fundamental ways. In addition, the microcircuitry, role of neuromodulators, and function of Area X are still unclear. Elucidating the mechanisms by which both mammalian-like and unique features of the AFP contribute to vocal learning may help lead to a broad understanding of the sensorimotor functions of basal ganglia circuits.

Introduction

The discovery that the “anterior forebrain pathway” (AFP; Fig. 1A) and surrounding brain areas in songbirds are homologous to mammalian basal ganglia circuits creates several opportunities and challenges (Doupe et al., 2005). This relationship allows the wealth of information gained from the study of primate and rodent basal ganglia circuits to guide research on the songbird AFP and the role it plays in vocal learning. For instance, the anatomy of mammalian basal ganglia circuits was informative in predicting the neurotransmitter used by the projection from Area X, a large nucleus of the AFP, to its thalamic target and the physiological properties of these Area X projection neurons (see below; Luo and Perkel, 1999a, Luo and Perkel, 1999b, Farries and Perkel, 2002). The organization of mammalian basal ganglia circuits continues to provide a framework for forming predictions about the unknown microcircuitry and neurochemistry of Area X. Of course, unanswered questions about the anatomy and function of mammalian basal ganglia circuits persist as well. The fact that the AFP is a basal ganglia circuit composed of discrete brain regions devoted to a single behavior makes it a promising model for understanding at least some aspects of how basal ganglia circuits work in general, including those in mammals during health and disease.

Although mammalian basal ganglia circuits and the AFP exhibit a number of striking similarities, it is important to continue asking precisely how similar they are. The last common ancestor of mammals and birds lived more than 300 million years ago (Kumar and Hedges, 1998). The degree to which a mechanistic understanding of the AFP might apply to understanding basal ganglia circuits in mammals and their role in motor learning hinges upon how much and in what ways the organization of songbird and mammalian basal ganglia circuits has diverged during this time of independent evolution. In this review we compare the anatomy of the AFP in songbirds to basal ganglia circuits in mammals. We describe several shared features and discuss some potentially important differences. We also consider whether there are any functional parallels between the AFP and mammalian basal ganglia circuits.

We first review the basic organization of mammalian basal ganglia circuits (see also Smith et al., 1998) before describing how it compares with that of the avian basal ganglia and in particular songbird Area X. The largest basal ganglia structure is the striatum, which receives glutamatergic input from much of the cerebral cortex and part of the thalamus. Most striatal neurons are medium spiny neurons. These cells are GABAergic and are the only cells that project out of the mammalian striatum. One class of spiny neuron projects to basal ganglia output structures—the internal segment of the globus pallidus (GPi; the rodent homologue of primate GPi is called the entopeduncular nucleus) and the substantia nigra pars reticulata (SNr). These structures contain tonically active GABAergic neurons that project to the thalamus or other structures outside of the basal ganglia (Fig. 1A). This “direct pathway” through the basal ganglia inhibits basal ganglia output. A second group of striatal spiny neurons initiates an “indirect pathway” by projecting to the external segment of the globus pallidus (GPe, or GP in rodents; Fig. 1B). GPe neurons are GABAergic and inhibit basal ganglia output (GPi and SNr) neurons via a direct connection and by inhibiting glutamatergic neurons in the subthalamic nucleus (STN) that project to the GPi and SNr. The STN also receives direct input from the cortex (the “hyperdirect pathway”). The net effect of activating the indirect or hyperdirect pathway is to increase the firing rate of basal ganglia output neurons. Similar basal ganglia pathways traverse the ventral striatum (nucleus accumbens) and the ventral pallidum (VP). The striatum receives dense dopaminergic innervation from the midbrain cell groups the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), and the SNc and VTA receive basal ganglia input from striatal spiny neurons, GPe, VP, and STN (Fig. 1C).