Brain Struct Funct DOI 10.1007/s00429-016-1250-9 REVIEW The functional logic of corticostriatal connections Stewart Shipp1,2 Received: 19 November 2015 / Accepted: 6 June 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Unidirectional connections from the cortex to neurochemical character, and onward circuitry. This is the the matrix of the corpus striatum initiate the cortico-basal basis of the classic direct and indirect pathway model of the ganglia (BG)-thalamocortical loop, thought to be important cortico-BG loop. Each pathway utilises a serial chain of in momentary action selection and in longer-term fine inhibition, with two such links, or three, providing positive tuning of behavioural repertoire; a discrete set of striatal and negative feedback, respectively. Operative co-activa- compartments, striosomes, has the complementary role of tion of direct and indirect SPNs is, therefore, pictured to registering or anticipating reward that shapes corticostriatal simultaneously promote action, and to restrain it. The plasticity. Re-entrant signals traversing the cortico-BG balance of this rival activity is determined by the contex- loop impact predominantly frontal cortices, conveyed tual inputs, which summarise the external and internal through topographically ordered output channels; by con- sensory environment, and the state of ongoing behavioural trast, striatal input signals originate from a far broader span priorities. Notably, the distributed sources of contextual of cortex, and are far more divergent in their termination. convergence upon a striatal locus mirror the transcortical The term ‘disclosed loop’ is introduced to describe this network harnessed by the origin of the operative input to organisation: a closed circuit that is open to outside influ- that locus, thereby capturing a similar set of contingencies ence at the initial stage of cortical input. The closed circuit relevant to determining action. The disclosed loop formu- component of corticostriatal afferents is newly dubbed lation of corticostriatal and subsequent BG loop circuitry, ‘operative’, as it is proposed to establish the bid for action as advanced here, refines the operating rationale of the selection on the part of an incipient cortical action plan; the classic model and allows the integration of more recent broader set of converging corticostriatal afferents is anatomical and physiological data, some of which can described as contextual. A corollary of this proposal is that appear at variance with the classic model. Equally, it every unit of the striatal volume, including the long, provides a lucid functional context for continuing cellular C-shaped tail of the caudate nucleus, should receive a studies of SPN biophysics and mechanisms of synaptic mandatory component of operative input, and hence plasticity. include at least one area of BG-recipient cortex amongst the sources of its corticostriatal afferents. Individual Keywords Basal ganglia Á Caudate Á Putamen Á operative afferents contact twin classes of GABAergic Corticostriatal Á Intratelencephalic Á Indirect pathway Á striatal projection neuron (SPN), distinguished by their Action value Á Medium spiny projection neuron Á Bridging collaterals & Stewart Shipp Abbreviations [email protected] BG Basal ganglia 1 Department of Visual Neuroscience, UCL Institute of GPe External globus pallidus Ophthalmology, Bath Street, London EC1V 9EL, UK GPi Internal globus pallidus 2 Stem Cell and Brain Research Institute, INSERM U1208, 18 SNr Substantia nigra pars reticulata Avenue Doyen Le´pine, 69675 Bron, France SNc Substantia nigra pars compacta 123 Brain Struct Funct SPN Striatal (spiny) projection neuron There is no single concept that adequately captures all STN Subthalamic nucleus known aspects of BG functionality. The proposal that the BG PT Corticostriatal neuron with axon passing into the play a role in action selection comes closest to this ideal, pyramidal tract especially if ‘action’ is extended to include cognitive events IT Corticostriatal neuron with axon remaining and emotional states, with the implicit idea that the BG act intratelencephalic upon prefrontal, limbic and motor cortex in analogous fashion (Mink 1996; Redgrave et al. 1999; Frank 2011). The Motor areas of cortex other principal functional dimension is learning, from simple M1 Primary motor cortex habit formation to complex motor sequences (Graybiel 1995; PMv Ventral premotor cortex Balleine et al. 2009; Jin and Costa 2015). Together these PMd Dorsal premotor cortex processes can be said to optimise behavioural repertoire in SMA Supplementary motor cortex pursuit of reward. The underlying neural plasticity hinges FEF Frontal eye field upon phasic dopamine release, signalling reward or its SEF Supplementary eye field expectation (Montague et al. 1996; Schultz 1998, 2013), and F2r Rostral premotor area F2 acting mainly within the striatum of the BG to enhance or F2c Caudal premotor area F2 depress synaptic strength (Centonze et al. 2001; Reynolds CMAc Caudal cingulate motor area and Wickens 2002). CMAr Rostral cingulate motor area This article will begin an analysis of BG function with a focus upon corticostriatal anatomy; it continues an occa- Other areas of cortex sional ‘Functional Logic’ series, aiming to discern func- LIP Lateral intraparietal area tional principles by characterising the structure and AIP Anterior intraparietal area organisation of neural circuits (Zeki and Shipp 1988; Shipp 2003). For the basal ganglia this is a challenging synthesis Motor thalamic nuclei indeed, given the accumulated density of research and the VA Ventral anterior multiplicity of functional dimensions it has uncovered. But VL Ventral lateral there are also well-thumbed blueprints of BG circuitry and MD Medial dorsal models of its operation on which to build. These are pre- sented in the following section, preceded by a brief sketch to help outline the division of labour between the present Introduction article and subsequent instalments. ‘Basal ganglia’ is the accepted collective term for a set of In a nutshell… structures in the basal forebrain, now known to form several parallel feedback loops with frontal cortex. In If the BG participates in action selection, this is not to register functional terms, there are just five principal components all the attendant details of the action or how it should be to the basal ganglia (BG), but they enjoy a rather richer executed. The BG circuitry need only receive a token rep- anatomical lexicon, whose mastery is the initial hurdle to resentation sufficient to indicate that the action in question a deeper appreciation of their fascinating inter-relation- has entered a state of planning. The purpose of the BG circuit ships. Take but one example: the substantia nigra and the is to evaluate its reward earning potential with respect to globus pallidus may be named for their contrasting dark alternative actions contingent upon all relevant factors; these and pale appearance, respectively, yet one BG compo- factors constitute the context of the action and include nent—its output module—is an amalgam of sub-parts interpretations of the sensory environment, internal states, from each. Figure 1 clarifies all such terminological and the planning status of other actions, either complemen- issues. The simplest conception of the BG loop is that the tary or alternative. We can refer to this token as a ‘bid’ lodged principal module receiving cortical input, the striatum, by a functional subunit of frontal cortex, whose salience directly feeds the BG output module, that communicates reflects the evaluated context, and which competes with the back to the cortex via the thalamus. As the initial corti- rival bids to traverse the BG circuit and bias cortical selection costriatal input is non-reciprocal, the loop as a whole is in favour of its parent plan. unidirectional, despite the presence of retro-connections at This, first stage of enquiry is to examine corticostriatal some stages (e.g. pallidostriatal, corticothalamic). The function: to consider how signals conveying a bid for action presence of additional, intrinsic BG nuclei provides for a selection or its context are distinguished, how context sep- variety of alternative loops through the system that are set arates into positive and negative reward contingencies and out below. how these may be evaluated. A subsequent stage will focus 123 Brain Struct Funct Corpus striatum Caudate nucleus INPUT Subthalamic NUCLEI nucleus Putamen (STN) INTRINSIC Globus Pallidus (GPe) pars compacta NUCLEI external segment (SNc) OUTPUT Globus Pallidus (GPi) pars reticulata NUCLEI internal segment (SNr) Pallidum Substantia nigra Fig. 1 Components of the basal ganglia. The diagram distinguishes continuous connectional topography, despite being quite separate the anatomical identity of nuclei (shown in blue ovals) from their anatomically. The subthalamic nucleus (STN) combines both extrin- functional role, as assessed by input/output connectivity (indicated by sic (cortical) and intrinsic inputs—the latter originating from another grey bands). The corpus striatum can be considered a single nucleus, intrinsic nucleus, the external segment of the globus pallidus (GPe). perforated by the internal capsule, and named for the strands of grey Finally, the substantia nigra pars compacta (SNc) has reciprocal matter that stretch between the caudate and putamen. The caudate is connections with the striatum, though it also receives extrinsic inputs. typically