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Nature Neuroscience Jan 2020Theories stipulate that memories are encoded within networks of cortical projection neurons. Conversely, GABAergic interneurons are thought to function primarily to...
Theories stipulate that memories are encoded within networks of cortical projection neurons. Conversely, GABAergic interneurons are thought to function primarily to inhibit projection neurons and thereby impose network gain control, an important but purely modulatory role. Here we show in male mice that associative fear learning potentiates synaptic transmission and cue-specific activity of medial prefrontal cortex somatostatin (SST) interneurons and that activation of these cells controls both memory encoding and expression. Furthermore, the synaptic organization of SST and parvalbumin interneurons provides a potential circuit basis for SST interneuron-evoked disinhibition of medial prefrontal cortex output neurons and recruitment of remote brain regions associated with defensive behavior. These data suggest that, rather than constrain mnemonic processing, potentiation of SST interneuron activity represents an important causal mechanism for conditioned fear.
Topics: Animals; Association Learning; Fear; Interneurons; Male; Memory; Mice; Mice, Inbred C57BL; Prefrontal Cortex; Somatostatin; Synaptic Transmission
PubMed: 31844314
DOI: 10.1038/s41593-019-0552-7 -
Nature Reviews. Neuroscience Oct 2019Discoveries over the past two decades demonstrate that regions distributed throughout the association cortex, often called the default network, are suppressed during... (Review)
Review
Discoveries over the past two decades demonstrate that regions distributed throughout the association cortex, often called the default network, are suppressed during tasks that demand external attention and are active during remembering, envisioning the future and making social inferences. This Review describes progress in understanding the organization and function of networks embedded within these association regions. Detailed high-resolution analyses of single individuals suggest that the default network is not a single network, as historically described, but instead comprises multiple interwoven networks. The multiple networks share a common organizational motif (also evident in marmoset and macaque anatomical circuits) that might support a general class of processing function dependent on internally constructed rather than externally constrained representations, with each separate interwoven network specialized for a distinct processing domain. Direct neuronal recordings in humans and monkeys reveal evidence for competitive relationships between the internally and externally oriented networks. Findings from rodent studies suggest that the thalamus might be essential to controlling which networks are engaged through specialized thalamic reticular neurons, including antagonistic subpopulations. These association networks (and presumably thalamocortical circuits) are expanded in humans and might be particularly vulnerable to dysregulation implicated in mental illness.
Topics: Animals; Association Learning; Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Nerve Net
PubMed: 31492945
DOI: 10.1038/s41583-019-0212-7 -
Frontiers in Neuroscience 2023Accumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the...
BACKGROUND
Accumulating evidence of clinical and neuroimaging studies indicated that migraine is related to brain structural alterations. However, it is still not clear whether the associations of brain structural alterations with migraine are likely to be causal, or could be explained by reverse causality confounding.
METHODS
We carried on a bidirectional Mendelian randomization analysis in order to identify the causal relationship between brain structures and migraine risk. Summary-level data and independent variants used as instruments came from large genome-wide association studies of total surface area and average thickness of cortex (33,992 participants), gray matter volume (8,428 participants), white matter hyperintensities (50,970 participants), hippocampal volume (33,536 participants), and migraine (102,084 cases and 771,257 controls).
RESULTS
We identified suggestive associations of the decreased surface area (OR = 0.85; 95% CI, 0.75-0.96; = 0.007), and decreased hippocampal volume (OR = 0.74; 95% CI, 0.55-1.00; = 0.047) with higher migraine risk. We did not find any significant association of gray matter volume, cortical thickness, or white matter hyperintensities with migraine. No evidence supporting the significant association was found in the reverse MR analysis.
CONCLUSION
We provided suggestive evidence that surface area and hippocampal volume are causally associated with migraine risk.
PubMed: 36937660
DOI: 10.3389/fnins.2023.1148458 -
Molecular Neurobiology Mar 2024Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain...
Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain structure in vivo and the transcriptome-driven functional basis with relevance to neurodegenerative disorders remains elusive. The aim of the present study is to identify the association among inflammation, brain structure, and neurodegenerative disorders at genetic and transcriptomic levels. Genetic variants associated with inflammatory cytokines were selected from the latest and largest genome-wide association studies of European ancestry. Neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and dementia with Lewy bodies (DLB) and brain structure imaging measures were selected as the outcomes. Two-sample Mendelian randomization analyses were conducted to identify the causal associations. Single-nucleus transcriptome data of the occipitotemporal cortex was further analyzed to identify the differential expressed genes in AD, which were tested for biological processes and protein interaction network. MR analysis indicated that genetically predicted TREM2 and sTREM2 were significantly associated with AD (TREM2: z-score = -9.088, p-value = 1.02 × 10; sTREM2: z-score = -7.495, p-value = 6.61 × 10). The present study found no evidence to support the causal associations between other inflammatory cytokines and the risks of AD, PD, ALS, or DLB. Genetically predicted TREM2 was significantly associated with the cortical thickness of inferior temporal (z-score = -4.238, p-value = 2.26 × 10) and pole temporal (z-score = -4.549, p-value = 5.40 × 10). In the occipitotemporal cortex samples, microglia were the main source of TREM2 gene and showed increasing expression of genes associated with inflammation and immunity. The present study has leveraged genetic and transcriptomic data to identify the association among TREM2, temporal lobe, and AD and the underlying cellular and molecular basis, thus providing a new perspective on the role of TREM2 in AD and insights into the complex associations among inflammation, brain structure, and neurodegenerative disorders, particularly AD.
Topics: Humans; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Genome-Wide Association Study; Mendelian Randomization Analysis; Neurodegenerative Diseases; Parkinson Disease; Brain; Inflammation; Cytokines; Encephalitis
PubMed: 37736795
DOI: 10.1007/s12035-023-03648-6 -
Frontiers in Systems Neuroscience 2020The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement... (Review)
Review
The traditional cerebellum's role has been linked to the high computational demands for sensorimotor control. However, several findings have pointed to its involvement in executive and emotional functions in the last decades. First in 2009 and then, in 2016, we raised why we should consider the cerebellum when thinking about drug addiction. A decade later, mounting evidence strongly suggests the cerebellar involvement in this disorder. Nevertheless, direct evidence is still partial and related mainly to drug-induced reward memory, but recent results about cerebellar functions may provide new insights into its role in addiction. The present review does not intend to be a compelling revision on available findings, as we did in the two previous reviews. This minireview focuses on specific findings of the cerebellum's role in drug-related reward memories and the way ahead for future research. The results discussed here provide grounds for involving the cerebellar cortex's apical region in regulating behavior driven by drug-cue associations. They also suggest that the cerebellar cortex dysfunction may facilitate drug-induced learning by increasing glutamatergic output from the deep cerebellar nucleus (DCN) to the ventral tegmental area (VTA) and neural activity in its projecting areas.
PubMed: 33192350
DOI: 10.3389/fnsys.2020.586574 -
Journal of Cognitive Neuroscience Oct 2022If two associations share an item, one may be remembered at the expense of the other (BC recalled but not AB). Here, we identify the neural processes by which this...
If two associations share an item, one may be remembered at the expense of the other (BC recalled but not AB). Here, we identify the neural processes by which this competition materializes and is resolved. We analyzed fMRI signal while participants studied sets of pairs that reliably induced pair-to-pair associative interference, but which participants could not fully resolve. Precuneus activity tracked retrieval of previous pairs during study of later overlapping pairs. This retrieval apparently produced interference by diverting study resources from the currently displayed pair. However, when activity in ventromedial prefrontal cortex, as well as anterior subregions of the hippocampus, was present while the earlier pair had been studied, interference was reversed, and both pairs were likely to be recalled. Angular gyrus and mid-frontal activity were related to interference resolution once the participant had seen both pairs. Taken together, associations compete via precuneus-mediated competitive retrieval, but ventromedial prefrontal cortex may neutralize this by ensuring that when the earlier association is remembered while studying the later pair, memories of the two pairs can overcome interference likely via activity in mid-frontal cortex and angular gyrus.
Topics: Hippocampus; Humans; Magnetic Resonance Imaging; Mental Recall; Prefrontal Cortex
PubMed: 35939625
DOI: 10.1162/jocn_a_01900 -
Cortex; a Journal Devoted To the Study... Oct 2019Traditional neuroanatomical models of written word processing have proposed multiple parallel routes from the visual word form area to lateral temporal, inferior... (Review)
Review
Traditional neuroanatomical models of written word processing have proposed multiple parallel routes from the visual word form area to lateral temporal, inferior parietal and inferior frontal cortex. Here we hypothesize the existence of an alternative ventromedial occipitotemporal route that culminates in the left perirhinal cortex which codes for the learned association between a concrete written word and the entity it refers to. The hypothesis fits in a broader context that considers perirhinal cortex as a connector hub connecting sensory input with more widespread representations of its content. According to the hypothesis, perirhinal coding of the association between a concrete word and its referent relies on the same operational principles as the coding of paired associates by perirhinal neurons documented by electrophysiological recordings in nonhuman primates. The evidence for a role of human left perirhinal cortex in written word processing is primarily based on two sources: Direct electrophysiological recordings reveal responses to concrete written words compared to function words or nonword stimuli. Secondly, in humans, the conceptual similarity between concrete written words is reflected in the similarity of the activity patterns evoked by these words in perirhinal cortex. The hypothesis has clinical relevance: Patients with the semantic variant of primary progressive aphasia who have damage of the left perirhinal cortex among other anterior temporal regions, have surface alexia as one of their defining features, i.e. the inability to access meaning from written words. The hypothesis of an alternative, ventral occipitotemporal written word processing pathway aligns with the concept that written language processing builds upon pre-existing visual object processing mechanisms.
Topics: Brain Mapping; Cognition; Humans; Pattern Recognition, Visual; Temporal Lobe; Word Processing; Writing
PubMed: 31174078
DOI: 10.1016/j.cortex.2019.05.002 -
Science (New York, N.Y.) Nov 2020The sensory neocortex is a critical substrate for memory. Despite its strong connection with the thalamus, the role of direct thalamocortical communication in memory...
The sensory neocortex is a critical substrate for memory. Despite its strong connection with the thalamus, the role of direct thalamocortical communication in memory remains elusive. We performed chronic in vivo two-photon calcium imaging of thalamic synapses in mouse auditory cortex layer 1, a major locus of cortical associations. Combined with optogenetics, viral tracing, whole-cell recording, and computational modeling, we find that the higher-order thalamus is required for associative learning and transmits memory-related information that closely correlates with acquired behavioral relevance. In turn, these signals are tightly and dynamically controlled by local presynaptic inhibition. Our results not only identify the higher-order thalamus as a highly plastic source of cortical top-down information but also reveal a level of computational flexibility in layer 1 that goes far beyond hard-wired connectivity.
Topics: Animals; Association Learning; Auditory Cortex; Memory; Mice; Mice, Inbred C57BL; Neocortex; Neural Pathways; Optogenetics; Patch-Clamp Techniques; Synapses; Thalamus
PubMed: 33184213
DOI: 10.1126/science.abc2399 -
Cureus May 2021Awake craniotomy with intraoperative neurophysiological language mapping (INLM) is an established procedure for patients undergoing surgery to resection tumors in the...
Awake craniotomy with intraoperative neurophysiological language mapping (INLM) is an established procedure for patients undergoing surgery to resection tumors in the language cortex area. INLM and continuous neurophysiological monitoring allow assessment of the language function, which is not possible under general anesthesia. INLM of the brain areas provides a helpful tool to the operating surgeon in reducing the risks associated with tumor resection in the motor and language cortex. We present a literature review and the technical method used for INLM by utilizing direct electrical cortical stimulation. We also report the usefulness of INLM for evaluation of the language function during resection of cortical tumors, epilepsy foci, and arteriovenous malformations (AVMs) located near language areas. First, the central sulcus is identified by sensory mapping, followed by the motor cortex's identification by direct electrical cortical stimulation (DECS). Neurological assessment of the patient is done by auditory and visual feedback. The patient is asked to repeat numbers, days, words, sentences, read words, and name pictures during cortical stimulation. DECS may cause a slurring or speech arrest. Electrocorticography (ECoG) is also performed during cortical stimulation to identify any after-discharges. Examination of the patient occurs immediately after surgery, and then 24 hours, one week, six months, and 12 months postoperatively. Bipolar DECS for motor mapping with ECoG can safely and reliably be utilized to identify essential language areas with minimizing permanent language deficits and maximizing the extent of tumor resection.
PubMed: 34123657
DOI: 10.7759/cureus.14960