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

Stephanie Rudolph
Nov 8, 2023; 43:7554-7564
Symposium and Mini-Symposium

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

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

Kyle E. Mathewson
Mar 4, 2009; 29:2725-2732
BehavioralSystemsCognitive

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

Randy L. Buckner
Aug 24, 2005; 25:7709-7717
Neurobiology of Disease

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

Jennifer L. Zamanian
May 2, 2012; 32:6391-6410
Neurobiology of Disease

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

Martijn P. van den Heuvel
Nov 2, 2011; 31:15775-15786
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.

Recent visual experience heavily influences our visual perception, but how neuronal activity is reshaped to alter and improve perceptual discrimination remains unknown. We recorded from populations of neurons in visual cortical area V4 while two male rhesus macaque monkeys performed a natural image change detection task under different experience conditions. We found that maximizing the recent experience with a particular image led to an improvement in the ability to detect a change in that image. This improvement was associated with decreased neural responses to the image, consistent with neuronal changes previously seen in studies of adaptation and expectation. We found that the magnitude of behavioral improvement was correlated with the magnitude of response suppression. Furthermore, this suppression of activity led to an increase in signal separation, providing evidence that a reduction in activity can improve stimulus encoding. Within populations of neurons, greater recent experience was associated with decreased trial-to-trial shared variability, indicating that a reduction in variability is a key means by which experience influences perception. Taken together, the results of our study contribute to an understanding of how recent visual experience can shape our perception and behavior through modulating activity patterns in the mid-level visual cortex.

Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota–gut–brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.

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.

Serotonin modulates diverse phenotypes and functions including depressive, aggressive, impulsive, and feeding behaviors, all of which have reward-related components. To date, research has focused on understanding these effects by measuring and manipulating dorsal raphe serotonin neurons and using single-receptor approaches. These studies have led to a better understanding of the heterogeneity of serotonin actions on behavior; however, they leave open many questions about the timing and location of serotonin's actions modulating the neural circuits that drive these behaviors. Recent advances in genetically encoded fluorescent biosensors, including the GPCR activation-based sensor for serotonin (GRAB-5-HT), enable the measurement of serotonin release in mice on a timescale compatible with a single rewarding event without corelease confounds. Given substantial evidence from slice electrophysiology experiments showing that serotonin influences neural activity of the striatal circuitry, and the known role of the dorsal medial striatal (DMS) in reward-directed behavior, we focused on understanding the parameters and timing that govern serotonin release in the DMS in the context of reward consumption, external reward value, internal state, and cued reward. Overall, we found that serotonin release is associated with each of these and encodes reward anticipation, value, approach, and consumption in the DMS.

GABAergic neurons and GABA_A receptors (GABA_ARs) are critical elements of almost all neuronal circuits. Most GABA_ARs of the CNS are heteropentameric ion channels composed of two α, two β, and one subunits. These receptors serve as important drug targets for benzodiazepine (BDZ) site agonists, which potentiate the action of GABA at GABA_ARs. Most GABA_AR classifications rely on the heterogeneity of the α subunit (α1–α6) included in the receptor complex. Heterogeneity of the subunits (1–3), which mediate synaptic clustering of GABA_ARs and contribute, together with α subunits, to the benzodiazepine (BDZ) binding site, has gained less attention, mainly because 2 subunits greatly outnumber the other subunits in most brain regions. Here, we have investigated a potential role of non-2 GABA_ARs in neural circuits of the spinal dorsal horn, a key site of nociceptive processing. Female and male mice were studied. We demonstrate that besides 2 subunits, 1 subunits are significantly expressed in the spinal dorsal horn, especially in its superficial layers. Unlike global 2 subunit deletion, which is lethal, spinal cord-specific loss of 2 subunits was well tolerated. GABA_AR clustering in the superficial dorsal horn remained largely unaffected and antihyperalgesic actions of HZ-166, a nonsedative BDZ site agonist, were partially retained. Our results thus suggest that the superficial dorsal horn harbors functionally relevant amounts of 1 subunits that support the synaptic clustering of GABA_ARs in this site. They further suggest that 1 containing GABA_ARs contribute to the spinal control of nociceptive information flow.