What Is the Role of the Intralaminar Thalamic Input to the Striatum and Its Potential Implications in Parkinson Disease?

Over the past several years, there has been an increased interest on the functional organization of the thalamic inputs to the basal ganglia.¹ Of particular relevance are inputs from the intralaminar nuclei targeting the striatum (Figure).^2-5 The intralaminar nuclei encompass several groups, anterior, central, and posterior, each consisting of several nuclei. The central intralaminar group, including the centromedian (CMn) and parafascicular (PF) nuclei (often combined as CMn/PF complex in primates and corresponding to the PF nucleus in rodents), provide the most abundant thalamic projections to the striatum^2,6,7 and participate in parallel basal ganglia-thalamocortical circuits controlling both motor and nonmotor functions.^5,8 The striatum also receives inputs from neurons in the anterior intralaminar nuclei, including the centrolateral nucleus (CL), which provides an important relay of inputs from the cerebellum to the striatum.^9,10 Viral tracing studies in transgenic rodents show a highly specific pattern of thalamic inputs to subtypes of striatal projection neurons and interneurons and the interaction between thalamostriatal and corticostriatal inputs.^3,11-13 Electrophysiologic recordings have provided insight into the effects of these thalamostriatal projections on attention, behavioral switching, reward responses, and motor control.^14-17 The intralaminar nuclei are affected in Parkinson disease (PD).^18-20 Studies in experimental models indicate that abnormal plasticity of the thalamostriatal system may contribute to motor manifestations of this disorder,^21-24 thus suggesting potential therapeutic targets.²⁵ For example, deep brain stimulation (DBS) of the CMn nucleus has been reported to improve levodopa-induced dyskinesias and freezing^26,27 and tremor^28,29 in patients with severe PD. Whereas the focus of this brief review is on the thalamostriatal projections from the intralaminar nuclei, the CMn and other thalamic nuclei also project to the globus pallidus (GP), substantia nigra (SN), and subthalamic nucleus (STN); these projections may also have a major role in PD.¹ The CMn nucleus has also received particular interest as a target for DBS in other disorders such as intractable epilepsy,^30-32 Tourette syndrome,^33,34 minimal conscious state,³⁵ and chronic pain.³⁶ These topics have been recently reviewed³⁷ and will not be discussed further in this study.