Marloes J. A. G. Henckens
Aug 12, 2009; 29:10111-10119
BehavioralSystemsCognitive

Xinying Guo
Oct 23, 2024; 44:e0727242024-e0727242024
Cellular

Rafael G. Almeida
Oct 18, 2017; 37:10023-10034
Viewpoints

Guo-qiang Bi
Dec 15, 1998; 18:10464-10472
Articles

Yang Hu
Feb 24, 2021; 41:1699-1715
BehavioralSystemsCognitive

Mahsa Altafi
Oct 23, 2024; 44:e0518242024-e0518242024
Systems/Circuits

Christelle Anaclet
Dec 12, 2012; 32:17970-17976
BehavioralSystemsCognitive

Elena Neumann
Oct 9, 2024; 44:e0591242024-e0591242024
Systems/Circuits

Robbert Havekes
Dec 12, 2012; 32:18137-18149
BehavioralSystemsCognitive

Laura Medlock
Apr 13, 2022; 42:3133-3149
Systems/Circuits

Michele Deodato
Oct 2, 2024; 44:e2308232024-e2308232024
BehavioralSystemsCognitive

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

Yasmin L. Hurd
Oct 16, 2019; 39:8250-8258
Symposium and Mini-Symposium

Lindsay P. Cameron
Nov 8, 2023; 43:7472-7482
Symposium and Mini-Symposium

Krista L. Hyde
Mar 11, 2009; 29:3019-3025
Development Plasticity Repair

Bruce S. McEwen
Jan 2, 2020; 40:12-21
Viewpoints

Tessa E.S. Charlesworth
Sep 11, 2019; 39:7228-7243
Viewpoints

Fadel Zeidan
Nov 18, 2015; 35:15307-15325
BehavioralSystemsCognitive

Nora D. Volkow
Dec 1, 2001; 21:9414-9418
Behavioral

Corey M. Ziemba
Oct 16, 2024; 44:e0349242024-e0349242024
Systems/Circuits

Jesse J. Langille
Jul 3, 2019; 39:5244-5246
Journal Club

Evdokia Menelaou
Aug 8, 2012; 32:10925-10939
BehavioralSystemsCognitive

Danilo De Gregorio
Feb 3, 2021; 41:891-900
Symposium and Mini-Symposium

Hannah Grotzinger
May 29, 2024; 44:e1856232024-e1856232024
BehavioralSystemsCognitive

Mitchell G. Spring
Oct 9, 2024; 44:e0602242024-e0602242024
BehavioralSystemsCognitive

Daniel Levenstein
Feb 15, 2023; 43:1074-1088
Viewpoints

William W. Seeley
Dec 11, 2019; 39:9878-9882
Progressions

Elle M. Murata
Sep 18, 2024; 44:e0573242024-e0573242024
BehavioralSystemsCognitive

Pietro Mazzoni
Apr 5, 2006; 26:3642-3645
BRIEF COMMUNICATION

Gijs Joost Brouwer
Nov 4, 2009; 29:13992-14003
BehavioralSystemsCognitive

AP Georgopoulos
Nov 1, 1982; 2:1527-1537
Articles

Bradley Voytek
Sep 23, 2015; 35:13257-13265
BehavioralSystemsCognitive

Uri Hasson
Mar 5, 2008; 28:2539-2550
BehavioralSystemsCognitive

Jordan A. Taylor
Feb 19, 2014; 34:3023-3032
BehavioralSystemsCognitive

John M. Beggs
Dec 3, 2003; 23:11167-11177
BehavioralSystemsCognitive

Shiaoching Gong
Sep 12, 2007; 27:9817-9823
Toolbox

Yulia Lerner
Feb 23, 2011; 31:2906-2915
BehavioralSystemsCognitive

Kong-Fatt Wong
Jan 25, 2006; 26:1314-1328
BehavioralSystemsCognitive

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Umut Güçlü
Jul 8, 2015; 35:10005-10014
BehavioralSystemsCognitive

Matthew F. Glasser
Aug 10, 2011; 31:11597-11616
BehavioralSystemsCognitive

During adolescence, cannabis experimentation is common, and its association with interindividual variations in brain maturation well studied. Cellular and molecular underpinnings of these system-level relationships are, however, unclear. We thus conducted a three-step study. First, we exposed adolescent male mice to -9-tetrahydrocannabinol (THC) or a synthetic cannabinoid WIN 55,212-2 (WIN) and assessed differentially expressed genes (DEGs), spine numbers, and dendritic complexity in their frontal cortex. Second, in human (male) adolescents, we examined group differences in cortical thickness in 34 brain regions, using magnetic resonance imaging, between those who experimented with cannabis before age 16 (n = 140) and those who did not (n = 327). Finally, we correlated spatially these group differences with gene expression of human homologs of mouse-identified DEGs. The spatial expression of 13 THC-related human homologs of DEGs correlated with cannabis-related variations in cortical thickness, and virtual histology revealed coexpression patterns of these 13 genes with cell-specific markers of astrocytes, microglia, and a type of pyramidal cells enriched in dendrite-regulating genes. Similarly, the spatial expression of 18 WIN-related human homologs of DEGs correlated with group differences in cortical thickness and showed coexpression patterns with the same three cell types. Gene ontology analysis indicated that 37 THC-related human homologs are enriched in neuron projection development, while 33 WIN-related homologs are enriched in processes associated with learning and memory. In mice, we observed spine loss and lower dendritic complexity in pyramidal cells of THC-exposed animals (vs controls). Experimentation with cannabis during adolescence may influence cortical thickness by impacting glutamatergic synapses and dendritic arborization.

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3α^A687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.

Targeting altered expression and/or activity of GABA (-aminobutyric acid) transporters (GATs) provide therapeutic benefit for age-related impairments, including cognitive dysfunction. However, the mechanisms underlying the transcriptional regulation of GATs are unknown. In the present study, we demonstrated that the stimulator of interferon genes (STING) upregulates GAT1 and GAT3 expression in the brain, which resulted in cognitive dysfunction. Genetic and pharmacological intervention of STING suppressed the expression of both GAT1 and GAT3, increased the ambient GABA concentration, and therefore, enhanced tonic GABA_A inhibition of principal hippocampal neurons, resulting in spatial learning and working memory deficits in mice in a type I interferon-independent manner. Stimulation of the STING->GAT pathway efficiently restored cognitive dysfunction in STING-deficient mice models. Our study uncovered for the first time that the STING signaling pathway regulates GAT expression in a cell autonomous manner and therefore could be a novel target for GABAergic cognitive deficits.

Emerging research in nonhuman animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white matter connectivity in a cohort of men and women using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections between the cerebellum and VTA predominantly originate in the right cerebellar hemisphere, interposed nucleus, and paravermal cortex and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared with other lobules. We discovered a mediolateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socioaffective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socioaffective regulation.