bioRxiv Subject Collection: Neuroscience's Journal
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Friday, March 22nd, 2024
| Time |
Event |
| 9:46a |
Kif7 deletion in a mouse model of human ciliopathy alters cerebral cortex development
Mutations of KIF7, a key ciliary component of the Sonic hedgehog (SHH) pathway, are associated in humans with malformations of the cerebral cortex and clinical features suggestive of cortical dysfunction. In both humans and mice, KIF7 regulates the processing of GLI-A and GLI3-R transcription factors in a SHH-dependent manner. To understand the pathological mechanisms involved in cerebral cortex defects, we took advantage of a Kif7 -/- mouse model in which the cellular mechanisms leading to the corpus callosum agenesis had already been investigated (Putoux et al, 2019). We observed a stronger impact of the Kif7 deletion on the development of the mouse dorsal cortex, in agreement with the important role of GLI3-R in the pattering of the dorsal telencephalon. The intermediate progenitor layer and cortical plate no longer segregated, preventing the formation of the intermediate zone, and subplate cells were missing. Corticofugal axons did not develop properly leading to a delayed colonization of the telencephalon by thalamo-cortical axons. These structural defects altered the cortical distribution of GABAergic interneurons generated in the basal telencephalon, which moreover exhibited intrinsic migration defects resembling those of control interneurons treated with cyclopamine. These migratory defaults suggested that the SHH pathway can no longer be activated in cortical interneurons generated in the ventral telencephalon of Kif7 -/- mice. | | 9:46a |
Neural dynamics express syntax in the time domain during natural story listening
Studies of perception have long shown that the brain adds information to its sensory analysis of the physical environment. A touchstone example for humans is language use: to comprehend a physical signal like speech, the brain must add linguistic knowledge, including syntax. Yet, syntactic rules and representations are atemporal (i.e., abstract and not bound by time), so they must be translated into time-varying signals for speech comprehension and production. Here, we test three different models of the temporal spell-out of syntactic structure against brain activity of people listening to Dutch stories: an integratory bottom-up parser, a predictive top-down parser, and a mildly predictive left-corner parser. These models build exactly the same structure but differ in when syntactic information is added by the brain - this difference is captured in the (temporal distribution of the) complexity metric incremental node count. Using temporal response function models with both acoustic and information-theoretic control predictors, node counts were regressed against source-reconstructed delta-band activity acquired with magnetoencephalography. Neural dynamics in left frontal and temporal regions most strongly reflect node counts derived by the top-down method, which postulates syntax early in time, suggesting that predictive structure building is an important component of Dutch sentence comprehension. The absence of strong effects of the left-corner model further suggests that its mildly predictive strategy does not represent Dutch language comprehension well, in contrast to what has been found for English. Understanding when the brain projects its knowledge of syntax onto speech, and whether this is done in language-specific ways, will inform and constrain the development of mechanistic models of syntactic-structure building in the brain. | | 4:18p |
GABA-ergic inhibition in human MT predicts visuo-spatial intelligence mediated by reverberation with frontal cortex
The canonical theory emphasizes fronto-parietal network (FPN) is key in mediating general fluid intelligence (gF). Meanwhile, recent studies show that multiple sensory regions in occipito-temporal border also play a key role in gF. However, the underlying mechanism is not yet clear. To investigate this issue, this study selects human MT complex (MT+), a region locates at the occipito-temporal border representing multiple sensory flows as a target brain area. Using ultra-high field magnetic resonance spectroscopy (MRS) to measure GABA/glutamate concentrations in MT+ combining resting-state fMRI functional connectivity (FC), behavioral examinations including MT+ perception suppression test and gF subtest in visuo-spatial component, we reveal that MT+ GABA and frontal-MT+ FC significantly correlate with the performance of visuo-spatial intelligence. Further, serial mediation model demonstrates that MT+ GABA predicting visuo-spatial gF fully mediated by reverberation effect between frontal and MT+ network. Our finding highlights that sensory cortex could integrate into complex cognition system as an intellectual hub. | | 4:18p |
Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices
The extensive long-range axonal projections of various classes of neocortical excitatory neurons are thought to contribute importantly to the highly integrative brain-wide interactions underlying the processing of sensory, cognitive and motor signals. Here, we investigated the long-range axonal output of various classes of genetically-defined projection neurons with cell bodies located in the whisker-related somatosensory cortices of the mouse through brain-wide light-sheet imaging of fluorescently-labeled axons segmented by specifically-trained convolutional networks quantified within the Allen Mouse Brain Atlas Common Coordinate Framework. We injected Cre-dependent virus to express GFP or tdTomato in the posterior primary somatosensory barrel cortex and the posterior supplemental somatosensory cortex, which contain the representations of the large posterior mystacial whiskers. We investigated the six following transgenic mouse lines: Rasgrf2-dCre, Scnn1a-Cre, Tlx3-Cre, Sim1-Cre, Rbp4-Cre and Ntsr1-Cre. We found long-range axonal projections in many diverse downstream brain areas with genetically-defined cell classes showing distinct innervation patterns. To test whether the revealed axonal projections might underpin functional circuits, we compared the spatial organization of the axonal innervation with functional connectivity maps obtained from optogenetic stimulation of sensory cortex and wide-field imaging of the activity propagation to frontal cortices. Both methods indicated that neurons located more laterally in somatosensory cortex topographically signaled to more anteriorly located regions in motor cortex. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling, and, together with further technological advances, this will help provide increasingly detailed connectivity information of the mouse brain, essential for understanding the complex neuronal circuitry underlying even simple goal-directed behaviors. |
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