Input- and Output-Specific Regulation of Serial Order Performance by Corticostriatal Circuits

• Published in: Neuron (Cambridge, Mass.) Mass.), 2015-10, Vol.88 (2), p.345-356
• Main Authors: Rothwell, Patrick E., Hayton, Scott J., Sun, Gordon L., Fuccillo, Marc V., Lim, Byung Kook, Malenka, Robert C.
• Format: Article
• Language: English
• Subjects: Animals; basal ganglia; Behavior; circuit; Corpus Striatum - physiology; Dopamine; Excitatory Postsynaptic Potentials - physiology; Experiments; Male; medium spiny neuron; Mice; Mice, Inbred C57BL; Mice, Transgenic; motor cortex; Motor Cortex - physiology; mouse; Nerve Net - physiology; Neuronal Plasticity - physiology; optogenetics; Rodents; serial order; striatum; Surgery; synaptic plasticity
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.09.035

The serial ordering of individual movements into sequential patterns is thought to require synaptic plasticity within corticostriatal circuits that route information through the basal ganglia. We used genetically and anatomically targeted manipulations of specific circuit elements in mice to isolate the source and target of a corticostriatal synapse that regulates the performance of a serial order task. This excitatory synapse originates in secondary motor cortex, terminates on direct pathway medium spiny neurons in the dorsolateral striatum, and is strengthened by serial order learning. This experience-dependent and synapse-specific form of plasticity may sculpt the balance of activity in basal ganglia circuits during sequential movements, driving a disparity in striatal output that favors the direct pathway. This disparity is necessary for execution of responses in serial order, even though both direct and indirect pathways are active during movement initiation, suggesting dynamic modulation of corticostriatal circuitry contributes to the choreography of behavioral routines. •In a serial order task, secondary motor cortex input to striatum initiates responses•Striatal direct pathway is necessary for completion of responses in serial order•Serial order learning strengthens synapses connecting motor cortex and striatum•Task performance requires a disparity of striatal output favoring the direct pathway Many behaviors involve distinct movements performed in a specific serial order. Rothwell et al. show serial order performance is regulated by a monosynaptic pathway linking secondary motor cortex to striatal cells that form the direct pathway through the basal ganglia.