title: The mediodorsal thalamus drives feedforward inhibition in the anterior cingulate cortex via parvalbumin interneurons.
abstract: Although the medial prefrontal cortex (mPFC) is classically defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD), the nature of information transfer between MD and mPFC is poorly understood. In sensory thalamocortical pathways, thalamic recruitment of feedforward inhibition mediated by fast-spiking, putative parvalbumin-expressing (PV) interneurons is a key feature that enables cortical neurons to represent sensory stimuli with high temporal fidelity. Whether a similar circuit mechanism is in place for the projection from the MD (a higher-order thalamic nucleus that does not receive direct input from the periphery) to the mPFC is unknown. Here we show in mice that inputs from the MD drive disynaptic feedforward inhibition in the dorsal anterior cingulate cortex (dACC) subregion of the mPFC. In particular, we demonstrate that axons arising from MD neurons directly synapse onto and excite PV interneurons that in turn mediate feedforward inhibition of pyramidal neurons in layer 3 of the dACC. This feedforward inhibition in the dACC limits the time window during which pyramidal neurons integrate excitatory synaptic inputs and fire action potentials, but in a manner that allows for greater flexibility than in sensory cortex. These findings provide a foundation for understanding the role of MD-PFC circuit function in cognition.
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and.
authors: Kristen
authors: K
authors: Delevich
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, MSTP/Neuroscience Graduate Program, Stony Brook University, Stony Brook, New York 11790.
authors: Jason
authors: J
authors: Tucciarone
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and.
authors: Z Josh
authors: ZJ
authors: Huang
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and bli@cshl.edu.
authors: Bo
authors: http://orcid.org/0000-0002-0154-3088
authors: B
authors: Li
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D000075402:Channelrhodopsins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000166:cytology*; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020645:Mediodorsal Thalamic Nucleus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000075402:Channelrhodopsins; D004268:DNA-Binding Proteins; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D008164:Luminescent Proteins; D010320:Parvalbumins; D010852:Picrotoxin; D022661:RNA, Untranslated; D014157:Transcription Factors; C499942:Grhl3 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse
keywords: anterior cingulate cortex; feedforward inhibition; medial prefrontal cortex; mediodorsal thalamus; parvalbumin interneuron