Journal Article

A comprehensive excitatory input map of the striatum reveals novel functional organization

Hunnicutt, Barbara J, Zhong, Haining, Mao, Tianyi, Birdsong, William T, Jongbloets, Bart C, Gertz, Katrina J

2016

Overview

The striatum integrates excitatory inputs from the cortex and the thalamus to control diverse functions. Although the striatum is thought to consist of sensorimotor, associative and limbic domains, their precise demarcations and whether additional functional subdivisions exist remain unclear. How striatal inputs are differentially segregated into each domain is also poorly understood. This study presents a comprehensive map of the excitatory inputs to the mouse striatum. The input patterns reveal boundaries between the known striatal domains. The most posterior striatum likely represents the 4th functional subdivision, and the dorsomedial striatum integrates highly heterogeneous, multimodal inputs. The complete thalamo-cortico-striatal loop is also presented, which reveals that the thalamic subregions innervated by the basal ganglia preferentially interconnect with motor-related cortical areas. Optogenetic experiments show the subregion-specific heterogeneity in the synaptic properties of striatal inputs from both the cortex and the thalamus. This projectome will guide functional studies investigating diverse striatal functions. To fully understand how the brain works, we need to understand how different brain structures are organized and how information flows between these structures. For example, the cortex and thalamus communicate with another structure known as the basal ganglia, which is essential for controlling voluntary movement, emotions and reward behaviour in humans and other mammals. Information from the cortex and the thalamus enters the basal ganglia at an area called the striatum. This area is further divided into smaller functional regions known as domains that sort sensorimotor, emotion and executive information into the basal ganglia to control different types of behaviour. Three such domains have been identified in the striatum of mice. However, the boundaries between these domains are vague and it is not clear whether any other domains exist or if the domains can actually be divided into even smaller areas with more precise roles. Information entering the striatum from other parts of the brain can either stimulate activity in the striatum (known as an “excitatory input”) or alter existing excitatory inputs. Now, Hunnicutt et al. present the first comprehensive map of excitatory inputs into the striatum of mice. The experiments show that while many of the excitatory inputs flowing into the striatum from the cortex and thalamus are sorted into the three known domains, a unique combination of the excitatory inputs are sorted into a new domain instead. One of the original three domains of the striatum is known to relay information related to associative learning, for example, linking an emotion to a person or place. Hunnicutt et al. show that this domain has a more complex architecture than the other domains, being made up of many distinct areas. This complexity may help it to process the various types of information required to make such associations. The findings of Hunnicutt et al. provide a framework for understanding how the striatum works in healthy and diseased brains. Since faulty information processing in the striatum is a direct cause of Parkinson’s disease, Huntington’s disease and other neurological disorders in humans, this framework may aid the development of new treatments for these disorders.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Animals / Basal ganglia / Brain / Brain Mapping / Corpus Striatum - anatomy & histology / Corpus Striatum - physiology / corticostriatal projections / Data analysis / Datasets / Functional morphology / mesoscopic connectome / Mice / Neostriatum / Neural circuitry / Neuroscience / Observations / Optogenetics / Perceptual-motor processes / Physiological aspects / Sensorimotor system / Software / striatal circuitry / striatal subdivisions / Striatum / thalamostriatal projections / Thalamus