Connectional architecture of the prefrontal cortex in the marmoset brain

The primate prefrontal cortex (PFC) has greatly expanded to evolve specialized architecture, but its roles in top-down brain control remain enigmatic. Based on connectomics mapping of the marmoset PFC, we characterized two contrasting features of corticocortical and corticostriatal projections. One is the "focalness" of projections, exemplified by multiple columnar axonal terminations in the cortical layers and the other is the "widespreadness" of weaker projections, whose patterns consisted of several common motifs representing the framework of PFC connectivity. We clarified the topographic rules of distribution for these features, which should constrain how PFC neurons can coordinate to control the target regions as populations. These features are observed only primitively in rodents and are considered critical in understanding the roles of the PFC in neuropsychiatric disorders.

Corticostriatal control of defense behavior in mice induced by auditory looming cues

Animals exhibit innate defense behaviors in response to approaching threats cued by the dynamics of sensory inputs of various modalities. The underlying neural circuits have been mostly studied in the visual system, but remain unclear for other modalities. Here, by utilizing sounds with increasing (vs. decreasing) loudness to mimic looming (vs. receding) objects, we find that looming sounds elicit stereotypical sequential defensive reactions: freezing followed by flight. Both behaviors require the activity of auditory cortex, in particular the sustained type of responses, but are differentially mediated by corticostriatal projections primarily innervating D2 neurons in the tail of the striatum and corticocollicular projections to the superior colliculus, respectively. The behavioral transition from freezing to flight can be attributed to the differential temporal dynamics of the striatal and collicular neurons in their responses to looming sound stimuli. Our results reveal an essential role of the striatum in the innate defense control.

Corticostriatal Projections of Macaque Area 44

ABSTRACTVentrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. Yet, the corticostriatal circuitry that may contribute to area 44 functions is not clear, as prior investigation of area 44 corticostriatal projections is limited. Here, we used anterograde and retrograde tracing in macaques to map the innervation zone of area 44 corticostriatal projections, quantify their strengths, and evaluate their convergence with corticostriatal projections from non-motor and motor-related frontal regions. First, terminal fields from a rostral area 44 injection site were found primarily in the central caudate nucleus, whereas those from a caudal area 44 injection site were found primarily in the ventrolateral putamen. Second, amongst sampled striatal retrograde injection sites, area 44 input as a percentage of total frontal cortical input was highest in the ventral putamen at the level of the anterior commissure. Third, area 44 projections converged with both orofacial premotor area 6VR and other motor related projections (in the putamen), and with non-motor prefrontal projections (in the caudate nucleus). These findings support the role of area 44 as an interface between motor and non-motor functional domains, possibly facilitated by rostral and caudal area 44 subregions with distinct corticostriatal connectivity profiles.

Corticostriatal Projections of Macaque Area 44

Ventrolateral frontal area 44 is implicated in inhibitory motor functions and facilitating prefrontal control over vocalization. The contribution of corticostriatal circuits to area 44 functions is unclear, as prior investigation of area 44 projections to the striatum—a central structure in motor circuits—is limited. Here, we used anterograde and retrograde tracing in macaques to map the innervation zone of area 44 corticostriatal projections, quantify their strengths, and evaluate their convergence with corticostriatal projections from other frontal cortical regions. First, whereas terminal fields from a rostral area 44 injection site were found primarily in the central caudate nucleus, those from a caudal area 44 injection site were found primarily in the ventrolateral putamen. Second, amongst sampled injection sites, area 44 input as a percentage of total frontal cortical input was highest in the ventral putamen at the level of the anterior commissure. Third, area 44 projections converged with orofacial premotor area 6VR and other motor-related projections (in the putamen), and with nonmotor prefrontal projections (in the caudate nucleus). Findings support the role of area 44 as an interface between motor and nonmotor functional domains, possibly facilitated by rostral and caudal area 44 subregions with distinct corticostriatal connectivity profiles.

Cell type-specific variation of somatotopic precision across corticostriatal projections

The striatum shows general topographic organization and regional differences in behavioral functions. How corticostriatal topography differs across cortical areas and cell types to support these distinct functions is unclear. This study contrasted corticostriatal projections from two layer 5 cell types, intratelencephalic (IT-type) and pyramidal tract (PT-type) neurons, using viral vectors expressing fluorescent reporters in Cre-driver mice. Long-range corticostriatal projections from sensory and motor cortex are somatotopic, with a decreasing somatotopic specificity as injections move from sensory to motor and frontal areas. Somatotopic organization differs between IT-type and PT-type neurons, including injections in the same site, with IT-type neurons having higher somatotopic stereotypy than PT-type neurons. Furthermore, IT-type projections from interconnected cortical areas have stronger correlations in corticostriatal targeting than PT-type projections do. Thus, as predicted by a long-standing basal ganglia model, corticostriatal projections of interconnected cortical areas form parallel circuits in basal ganglia-thalamus-cortex loops.

The organization and dynamics of corticostriatal pathways link the medial orbitofrontal cortex to future behavioral responses

Accurately making a decision in the face of incongruent options increases the efficiency of making similar congruency decisions in the future. Contextual factors like reward can modulate this adaptive process, suggesting that networks associated with monitoring previous success and failure outcomes might contribute to this form of behavioral updating. To evaluate this possibility, a group of healthy adults ( n = 30) were tested with functional MRI (fMRI) while they performed a color-word Stroop task. In a conflict-related region of the medial orbitofrontal cortex (mOFC), stronger BOLD responses predicted faster response times (RTs) on the next trial. More importantly, the degree of behavioral adaptation of RTs was correlated with the magnitude of mOFC-RT associations on the previous trial, but only after accounting for network-level interactions with prefrontal and striatal regions. This suggests that congruency sequencing effects may rely on interactions between distributed corticostriatal circuits. This possibility was evaluated by measuring the convergence of white matter projections from frontal areas into the striatum with diffusion-weighted imaging. In these pathways, greater convergence of corticostriatal projections correlated with stronger functional mOFC-RT associations that, in turn, provided an indirect pathway linking anatomical structure to behavior. Thus distributed corticostriatal processing may mediate the orbitofrontal cortex's influence on behavioral updating, even in the absence of explicit rewards.