The mouse prefrontal cortex: Unity in diversity

The prefrontal cortex (PFC) is considered to constitute the highest stage of neural integration and be devoted representation production actions. Studies in primates have laid foundation for theories regarding principles function provided mechanistic insights. recent surge studies PFC mice holds promise evolvement present development novel concepts, particularly shared across mammals. Here we review empirical work on mouse capitalizing experimental toolbox currently privileged this species. We conclude that line research has revealed cellular structural distinctions neuronal activity with direct relevance functions PFC. foresee data-rich will key shed light general architecture mechanisms underlying cognitive aspects organized It been suggested unique characteristic feature ability structure serve future (Fuster, 2015Fuster J.M. cortex. Elsevier, 2015Crossref Google Scholar). This entails can represent goals access internal external information state. To reach a goal, should hold integrative adaptively utilizing manipulating representations provide “temporal gestalt” coordinated goal-directed actions relevant means, timescales, motives goal. must, furthermore, previous experiences appropriate prediction how different influence future. In addition, must functional means initiation execution These are mostly derived from humans non-human Standing shoulders giants; what do findings reveal about does? Technological advancements use behavioral tasks increased complexity put at forefront systems neuroscience field (Carandini Churchland, 2013Carandini M. Churchland A.K. Probing perceptual decisions rodents.Nat. Neurosci. 2013; 16: 824-831Crossref PubMed Scopus (149) Scholar; Luo et al., 2018Luo L. Callaway E.M. Svoboda K. Genetic Dissection Neural Circuits: A Decade Progress.Neuron. 2018; 98: 256-281Abstract Full Text PDF (150) Arguably, approaching point where mammalian species which most collective knowledge brain’s neurophysiology. Given extensive sophisticated data gathered date, it appears feasible approach description incorporates discoveries neurobiological features, including cell-type-specific gene expression profiles, whole-brain connectivity, processing. latest pertaining exclusively mice. string quantitative, large-scale connectivity strongly indicates presence module (Harris 2019Harris J.A. Mihalas S. Hirokawa K.E. Whitesell J.D. Choi H. Bernard A. Bohn P. Caldejon Casal Cho al.Hierarchical organization cortical thalamic connectivity.Nature. 2019; 575: 195-202Crossref (98) Scholar) likely encompassing three larger subdivisions partially overlapping brain connectivity. paints picture highly network receiving converging virtually whole brain. show interconnectivity between subregions very extensive, supporting view computations interdependent various networks common conducted synthesis past decade’s evidence segregation within found little specialization or hierarchical subregions, notion focusing solely localized insufficient potentially undermine our understanding because one “cannot see forest trees” (Wilson 2010Wilson C.R.E. Gaffan D. Browning P.G.F. Baxter M.G. Functional localization cortex: missing trees?.Trends 2010; 33: 533-540Abstract (0) highlight utility as an animal model study rich high-dimensional dynamics place particular emphasis patterns associated specific processes. Electrophysiological recordings, combination selected manipulation activity, insight into underpinnings local operations significance top-down (feedback) signals. Large-field imaging coordinates cortex-wide their temporal dynamics. not only align well current but also drive logic processing involving E pluribus unum (out many, one).—Fuster, Scholar Even when restricted Mus musculus (house mouse), term “PFC” cause Babylonian confusion; over century, nomenclature anatomical delineations subjected constant change (Box 1). strictly adhere Allen Reference Atlas (ARA) ontology (Wang 2020bWang Q. Ding S.-L. Li Y. Royall J. Feng Lesnar Graddis N. Naeemi Facer B. Ho al.The Mouse Brain Common Coordinate Framework: 3D Atlas.Cell. 2020; 181: 936-953.e20Abstract analyses figures unless stated otherwise; however, discussing published work, used respective preserved. long “defined” projection mediodorsal thalamus (MD) (Rose Woolsey, 1948Rose J.E. Woolsey C.N. orbitofrontal its connections nucleus rabbit, sheep cat.Res. Publ. Assoc. Res. Nerv. Ment. Dis. 1948; 27: 210-232PubMed MD projects frontal regions mouse, already original publication, “…the usefulness definition questioned” (Guldin 1981Guldin W.O. Pritzel Markowitsch H.J. Prefrontal defined area nucleus.Brain Behav. Evol. 1981; 19: 93-107Crossref Of 40–50 make up isocortex (Lein 2007Lein E.S. Hawrylycz M.J. Ao Ayres Bensinger Boe A.F. Boguski M.S. Brockway K.S. Byrnes E.J. al.Genome-wide atlas adult brain.Nature. 2007; 445: 168-176Crossref (3296) Scholar), PFC, and, more importantly, why? Cytoarchitectural criteria dominated parcellation, (a of) four characteristics best define regions: function, architecture, topography (Van Essen Glasser, 2018Van D.C. Glasser M.F. Parcellating Cerebral Cortex: How Invasive Animal Inform Noninvasive Mapmaking Humans.Neuron. 99: 640-663Abstract (42) Particularly focus large number decade, macaques (Ercsey-Ravasz 2013Ercsey-Ravasz Markov N.T. Lamy C. Van Knoblauch Toroczkai Z. Kennedy predictive cerebral based distance rule.Neuron. 80: 184-197Abstract (199) G?m?nu? 2018G?m?nu? R. Ercsey-Ravasz Burkhalter Cortical Connectome, Characterized by Ultra-Dense Graph, Maintains Specificity Distinct Connectivity Profiles.Neuron. 97: 698-715.e10Abstract identified modules (or cliques); i.e., dense interconnectivity. dedicated similar (Bullmore Sporns, 2009Bullmore E. Sporns O. Complex networks: graph theoretical analysis systems.Nat. Rev. 2009; 10: 186-198Crossref (6514) corticocortical patterns, six were identified, (the others being somatomotor, visual, auditory, medial, lateral modules, respectively) (Figures 1A 1B ; Harris prelimbic (PL), infralimbic (ILA), dorsal ventral anterior cingulate areas (ACAd, ACAv, respectively), pole, (FRP), orbital (lateral [ORBl], ventrolateral [ORBvl], medial [ORBm]) (Figure 1A). Importantly, disagrees anatomically (Oh 2014Oh S.W. Ng Winslow Cain Wang Lau Kuan Henry A.M. al.A mesoscale connectome 2014; 508: 207-214Crossref (1136) divisions agranular insular (AId, AIv, secondary motor (MOs) assigned module. However, AI MOs border share important degree vast region 1), described (Hira 2013Hira Ohkubo F. Tanaka Y.R. Masamizu Augustine G.J. Kasai Matsuzaki vivo optogenetic tracing forelimb areas.Front. Circuits. 7: 55Crossref (39) Komiyama 2010Komiyama T. Sato T.R. O’Connor D.H. Zhang Y.-X. Huber Hooks B.M. 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Neuwied, 1872Google long-standing tradition neuroscience. Brodmann, 1909Brodmann Vergleichende Lokalisationslehre Grosshirnrinde ihren Prinzipien dargestellt auf Grund des Zellenbaues von. Barth, 1909Google utilized cytoarchitecture parcellate his seminal delineation 52 primate He “frontal granular cortex” distinct layer 4 primates. completely agranular. Rose proposed could was shown non-primate Projections later demonstrated rats (Leonard, 1969Leonard C.M. rat. I. nucleus. II. Efferent connections.Brain 1969; 12: 321-343Crossref schematics portray targeted highlighting varying years (Caviness, 1975Caviness Jr., V.S. Architectonic map neocortex normal mouse.J. Comp. Neurol. 1975; 164: 247-263Crossref Franklin Praxinos, 2007Franklin K.B.J. Praxinos Stereotaxic Coordinates. Academic Press, 2007Google Hof 2000Hof P.R. Young W.G. Bloom F.E. Belichenko P.V. Celio M.R. Comparative 129/Sv Brains. 2000Google Lein Rose, 1929Rose Cytoarchitektonischer Groszhirne Maus.J. Psychol. 1929; 40: 1-51Google Uylings, 2014Van Comparison (stereotactic) parcellations cortex.Brain 219: 433-459Crossref (24) Wree 1983Wree Zilles Schleicher quantitative cytoarchitectonics. VIII. areal pattern albino mouse.Anat. Embryol. (Berl.). 1983; 166: 333-353Crossref (abbreviations publications). plotted borders individual atlases onto ARA plate 100960376 (anteroposterior AP, ~1.75 mm; 2011 coronal P56) recently CCFv3 (used Figure 3) again changed outline (also comparison updated Because stereotaxic indispensable experimentalists, inconsistencies surrounding contribute miscommunication While awaiting unified anatomy terminology reporting precise imperative.Figure 1Corticocortical defines mouseShow full caption(A) Matrix ipsilateral connection densities (normalized) 43 isocortical mouse. Top left corner: modularity metrics shuffled (Q Qshuffled, each ? level. resolution parameter. Colors row indicate community = 0–2.5. Community (module affiliation) determined independently value ?, colors matched communities split increases. Columns colored 1.3 (dashed line).(B) flattened color coded affiliation 1.3.(C) Intermodule diagram. output (colored dots) indicated curved lines module’s own color. edge width represents sum (A). Nodes positioned along single axis score. CC, neurons; TC, thalamocortical CT, corticothalamic neurons. Adapted Scholar.View Large Image ViewerDownload Hi-res image Download (PPT) Cytoarchitecture imperative. (A) line). (B) 1.3. (C) Scholar. When conceptualizing Hubel Wiesel, 1962Hubel Wiesel T.N. Receptive fields, binocular interaction cat’s visual cortex.J. Physiol. 1962; 160: 106-154Crossref (8098) theorized importance determining circuit it. Similarly, Rockland Pandya, 1979Rockland Pandya D.N. Laminar origins terminations occipital lobe rhesus monkey.Brain 1979; 179: 3-20Crossref (666) criterion (i.e., regional laminar relationship neurons’ soma axon terminals) delineate order monkey. have, studies, acted framework identification hierarchy purely aforementioned performed Institute Science deciphered. nearly all traced, terminals target mapped. For unbiased ordering regions, index defining predominant efferent (feedback feedforward) generated. displayed holding proportion feedback projections; 1C; Instruct