The song system of oscine birds has frequently been presented as a model system for motor learning in vertebrates. This practice has been bolstered by the growing recognition that one part of the song system that is essential for song learning, area X, is a component of the avian striatum. The mammalian striatum, the input structure of the basal ganglia, has been implicated in a number of motor-related functions, including motor learning, suggesting that song learning in birds and motor learning in mammals may use similar physiological mechanisms. We studied the intrinsic physiological properties of area X neurons in brain slices to see how closely they match properties identified in mammalian striatal neurons and to collect data that are necessary to understand how area X processes information. We found that area X contains all four physiological cell types present in the mammalian striatum and that each is very similar to its mammalian counterpart. We also found a fifth cell type in area X that has not been reported in mammalian striatum; instead, this cell type resembles neurons that have been recorded in the mammalian globus pallidus. This pallidum-like cell type morphologically resembles the projection neurons of area X. We suggest that area X contains a pathway equivalent to the "direct" striatopallidothalamic pathway through the mammalian basal ganglia, with the striatal and pallidal components intermingled in one nucleus.

Area X is a songbird basal ganglia nucleus that is required for vocal learning. Both Area X and its immediate surround, the medial striatum (MSt), contain cells displaying either striatal or pallidal characteristics. We used pathway-tracing techniques to compare directly the targets of Area X and MSt with those of the lateral striatum (LSt) and globus pallidus (GP). We found that the zebra finch LSt projects to the GP, substantia nigra pars reticulata (SNr) and pars compacta (SNc), but not the thalamus. The GP is reciprocally connected with the subthalamic nucleus (STN) and projects to the SNr and motor thalamus analog, the ventral intermediate area (VIA). In contrast to the LSt, Area X and surrounding MSt project to the ventral pallidum (VP) and dorsal thalamus via pallidal-like neurons. A dorsal strip of the MSt contains spiny neurons that project to the VP. The MSt, but not Area X, projects to the ventral tegmental area (VTA) and SNc, but neither MSt nor Area X projects to the SNr. Largely distinct populations of SNc and VTA dopaminergic neurons innervate Area X and surrounding the MSt. Finally, we provide evidence consistent with an indirect pathway from the cerebellum to the basal ganglia, including Area X. Area X projections thus differ from those of the GP and LSt, but are similar to those of the MSt. These data clarify the relationships among different portions of the oscine basal ganglia as well as among the basal ganglia of birds and mammals.

Farries MA, Fairhall AL. Reinforcement learning with modulated spike timing-dependent synaptic plasticity. J Neurophysiol 98: 3648 -3665, 2007. First published October 10, 2007; doi:10.1152/jn.00364.2007. Spike timing-dependent synaptic plasticity (STDP) has emerged as the preferred framework linking patterns of pre-and postsynaptic activity to changes in synaptic strength. Although synaptic plasticity is widely believed to be a major component of learning, it is unclear how STDP itself could serve as a mechanism for general purpose learning. On the other hand, algorithms for reinforcement learning work on a wide variety of problems, but lack an experimentally established neural implementation. Here, we combine these paradigms in a novel model in which a modified version of STDP achieves reinforcement learning. We build this model in stages, identifying a minimal set of conditions needed to make it work. Using a performance-modulated modification of STDP in a two-layer feedforward network, we can train output neurons to generate arbitrarily selected spike trains or population responses. Furthermore, a given network can learn distinct responses to several different input patterns. We also describe in detail how this model might be implemented biologically. Thus our model offers a novel and biologically plausible implementation of reinforcement learning that is capable of training a neural population to produce a very wide range of possible mappings between synaptic input and spiking output. I N T R O D U C T I O NSynaptic plasticity is widely believed to be at least a component of the neurobiological changes underlying learning, but it is still far from clear exactly how the forms of synaptic plasticity studied in vitro contribute to learning and memory. An early problem was that many protocols used to induce synaptic plasticity in vitro, such as tetanic stimulation (Andersen et al. 1977), were difficult to translate into precise plasticity rules. This left the modeler with a great deal of freedom in formulating plasticity rules that were "consistent" with experimental data, leaving considerable doubt as to which rules might accurately represent processes occurring in vivo. Over the last few years, new protocols for inducing synaptic plasticity in vitro have been devised that more closely emulate processes that might occur in the intact nervous system. Spike timing-dependent plasticity (STDP) is a prominent example of such a protocol. In STDP, synaptic changes are induced by repeatedly pairing presynaptic and postsynaptic action potentials (APs) with precisely controlled timing. At glutamatergic synapses in the isocortex and hippocampus, postsynaptic APs arriving after the onset of presynaptically evoked excitatory postsynaptic potentials (EPSPs) induce long-term potentiation (LTP) of that synapse (Fig. 1A), whereas APs arriving before EPSPs induce long-term depression (LTD) (Bi and Poo 1998;Debanne et al. 1998;Feldman 2000;Froemke and Dan 2002;Markram et al. 1997). Although much remains to be discovered about h...

Song learning in oscine birds relies on a circuit known as the "anterior forebrain pathway," which includes a specialized region of the avian basal ganglia. This region, area X, is embedded within a telencephalic structure considered homologous to the striatum, the input structure of the mammalian basal ganglia. Area X has many features in common with the mammalian striatum, yet has distinctive traits, including largely aspiny projection neurons that directly innervate the thalamus and a cell type that physiologically resembles neurons recorded in the mammalian globus pallidus. We have proposed that area X is a mixture of striatum and globus pallidus and has the same functional organization as circuits in the mammalian basal ganglia. Using electrophysiological and anatomical approaches, we found that area X contains a functional analog of the "direct" striatopallidothalamic pathway of mammals: axons of the striatal spiny neurons make close contacts on the somata and dendrites of pallidal cells. A subset of pallidal neurons project directly to the thalamus. Surprisingly, we found evidence that many pallidal cells may not project to the thalamus, but rather participate in a functional analog of the mammalian "indirect" pathway, which may oppose the effects of the direct pathway. Our results deepen our understanding of how information flows through area X and provide more support for the notion that song learning in oscines employs physiological mechanisms similar to basal ganglia-dependent forms of motor learning in mammals.

The subthalamic nucleus (STN) provides a second entry point for cortical input to the basal ganglia, supplementing the corticostriatal pathway. We examined the way intrinsic properties shape the response of the STN to cortical excitation, recording from rat STN in vivo and in brain slices. STN cells exhibited a near-zero slope conductance-and hence an effectively infinite membrane time constant-at subthreshold potentials. This makes STN cells exceptional temporal integrators, consistent with the common view that basal ganglia nuclei use rate coding. However, STN cells also exhibited a drop in spike threshold triggered by larger EPSPs, allowing them to fire time-locked spikes in response to coincident input. In addition to promoting coincidence detection, the threshold dynamics associated with larger EPSPs reduced the probability of firing spikes outside of a narrow window immediately after the stimulus, even on trials in which the EPSP did not directly trigger a spike. This shift in stimulus-evoked firing pattern would allow downstream structures to distinguish coincidence-triggered spikes from other spikes and thereby permit coincidence detection and rate coding to operate in parallel in the same cell. Thus, STN cells can combine two functions-integration and coincidence detection-that are normally considered mutually exclusive. This could support rapid communication between cortex and basal ganglia targets that bypasses the striatum without disrupting slower rate coding pathways.

The basal ganglia (BG) recipient thalamus controls motor output but it remains unclear how its activity is regulated. Several studies report that thalamic activation occurs via disinhibition during pauses in the firing of inhibitory pallidal inputs from the BG. Other studies indicate that thalamic spiking is triggered by pallidal inputs via post-inhibitory ‘rebound’ calcium spikes. Finally excitatory cortical inputs can drive thalamic activity, which becomes entrained, or time-locked, to pallidal spikes. We present a unifying framework where these seemingly distinct results arise from a continuum of thalamic firing ‘modes’ controlled by excitatory inputs. We provide a mechanistic explanation for paradoxical pallidothalamic coactivations observed during behavior and raise new questions of what information is integrated in the thalamus to control behavior.

The oscine song system has emerged as one of the leading model systems for studying motor learning in vertebrates, combining an easily recorded behavior with a discrete neural substrate. That neural substrate seems to be distinct from other structures in the avian brain and thus is often studied in isolation. However, the song system is unlikely to have evolved ex nihilo, and should share some features with the parts of the avian brain from which it evolved. Identification of its evolutionary precursors should help us apply what we know about the song system to other vertebrate motor systems, and vice versa. Here, I review the homologies between parts of the avian and mammalian telencephala and explain where the song system nuclei reside in this context. The organization of the song system is then compared to other parts of the avian brain and the brains of nonoscine birds. Study of the nonoscine brain has revealed a ‘general motor pathway’ from caudolateral neostriatum (NCL) to intermediate archistriatum (Ai) that resembles the song system motor pathway in its anatomical organization. No part of this motor pathway projects directly to brainstem vocal or respiratory centers in nonoscines, but it does innervate a wide variety of motor and premotor neuron populations that mediate other behaviors. This general motor pathway may be accompanied by an ‘anterior forebrain pathway’ , suggesting that the song system is simply a specialization of a part of this preexisting circuit. This hypothesis has implications for how accessory structures of the song system (e.g. HVc shelf, LMAN shell) are regarded, can help explain how the forebrain vocal control systems of three avian taxa (parrots, hummingbirds, and songbirds) could have evolved independently yet be so similar in organization, and makes testable predictions concerning the anatomy of the song system and the nonoscine brain.

Histological and morphological studies indicate that approximately 5% of striatal neurons are cholinergic or γ-aminobutyric acidergic (GABAergic) interneurons (gINs). However, the number of striatal neurons expressing known interneuron markers is too small to account for the entire interneuron population. We therefore studied the serotonin (5HT) receptor 3a-enhanced green fluorescent protein (5HT3a(EGFP)) mouse, in which we found that a large number of striatal gINs are labeled. Roughly 20% of 5HT3a(EGFP)-positive cells co-express parvalbumin and exhibit fast-spiking (FS) electrophysiological properties. However, the majority of labeled neurons do not overlap with known molecular interneuron markers. Intrinsic electrical properties reveal at least 2 distinct novel subtypes: a late-spiking (LS) neuropeptide-Y (NPY)-negative neurogliaform (NGF) interneuron, and a large heterogeneous population with several features resembling low-threshold-spiking (LTS) interneurons that do not express somatostatin, NPY, or neuronal nitric oxide synthase. Although the 5HT3a(EGFP) NGF and LTS-like interneurons have electrophysiological properties similar to previously described populations, they are pharmacologically distinct. In direct contrast to previously described NPY(+) LTS and NGF cells, LTS-like 5HT3a(EGFP) cells show robust responses to nicotine administration, while the 5HT3a(EGFP) NGF cell type shows little or no response. By constructing a molecular map of the overlap between these novel populations and existing interneuron populations, we are able to reconcile the morphological and molecular estimates of striatal interneuron numbers.