scholarly journals Neuropathologic features associated with basal forebrain atrophy in Alzheimer disease

Neurology ◽  
2020 ◽  
Vol 95 (10) ◽  
pp. e1301-e1311
Author(s):  
Stefan J. Teipel ◽  
H.-Christian Fritz ◽  
Michel J. Grothe ◽  
Keyword(s):  
Alzheimer Disease ◽  
Basal Forebrain ◽  
Gray Matter Volume ◽  
Region Of Interest ◽  
Brain Regions ◽  
Nucleus Basalis ◽  
Parahippocampal Gyrus ◽  
Brain Scans ◽  
Cholinergic Basal Forebrain ◽  
False Discovery

ObjectiveTo study the neuropathologic correlates of cholinergic basal forebrain (BF) atrophy as determined using antemortem MRI in the Alzheimer disease (AD) spectrum.MethodsWe determined associations between BF volume from antemortem MRI brain scans and postmortem assessment of neuropathologic features, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy body (LB) pathology, and TDP-43, in 64 cases of the Alzheimer's Disease Neuroimaging Initiative cohort. For comparison, we assessed neuropathologic features associated with hippocampal and parahippocampal gyrus atrophy. In addition to region of interest–based analysis, we determined the association of neuropathologic features with whole brain gray matter volume using regionally unbiased voxel-based volumetry.ResultsBF atrophy was associated with Thal amyloid phases (95% confidence interval [CI] −0.49 to −0.01, p = 0.049) and presence of LB pathology (95% CI −0.54 to −0.06, p = 0.015), as well as with the degree of LB pathology within the nucleus basalis Meynert (95% CI −0.54 to −0.07, p = 0.025). These effects were no longer significant after false discovery rate (FDR) correction. Hippocampal atrophy was significantly associated with the presence of TDP-43 pathology (95% CI −0.61 to −0.17, p = 0.003; surviving FDR correction), in addition to dentate gyrus NFT load (95% CI −0.49 to −0.01, p = 0.044; uncorrected). Voxel-based analysis confirmed spatially restricted effects of Thal phases and presence of LB pathology on BF volume.ConclusionsThese findings indicate that neuropathologic correlates of regional atrophy differ substantially between different brain regions that are typically involved in AD-related neurodegeneration, including different susceptibilities to common comorbid pathologies.

scholarly journals A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Blaise Robert ◽  
Eyal Y Kimchi ◽  
Yurika Watanabe ◽  
Tatenda Chakoma ◽  
Miao Jing ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Behavioral Outcomes ◽  
Cholinergic Neurons ◽  
Brain Regions ◽  
Brain State ◽  
Cholinergic Basal Forebrain ◽  
Diagonal Band ◽  
Orofacial Movements ◽  
Functional Topography ◽  
Global Brain

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a one-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.

scholarly journals α7 Nicotinic Receptor Up-regulation in Cholinergic Basal Forebrain Neurons in Alzheimer Disease

2007 ◽  
Vol 64 (12) ◽  
pp. 1771 ◽  
Author(s):  
Scott E. Counts ◽  
Bin He ◽  
Shaoli Che ◽  
Milos D. Ikonomovic ◽  
Steven T. DeKosky ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Basal Forebrain ◽  
Nicotinic Receptor ◽  
Cholinergic Basal Forebrain ◽  
Forebrain Neurons

scholarly journals Basal forebrain cholinergic neurons are part of the threat memory engram

2021 ◽  
Author(s):  
Prithviraj Rajebhosale ◽  
Mala R Ananth ◽  
Richard B Crouse ◽  
Li Jiang ◽  
Gretchen López- Hernández ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Basolateral Amygdala ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Early Gene ◽  
Intrinsic Excitability ◽  
Cholinergic Basal Forebrain ◽  
Basal Forebrain Cholinergic Neurons ◽  
Cholinergic Signaling ◽  
Memory Engram

Although the engagement of cholinergic signaling in threat memory is well established (Knox, 2016a), our finding that specific cholinergic neurons are requisite partners in a threat memory engram is likely to surprise many. Neurons of the basal forebrain nucleus basalis and substantia innonimata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA), whose activation are required for both the acquisition and retrieval of cued threat memory and innate threat response behavior. The retrieval of threat memory by the presentation of the conditioning tone alone elicits acetylcholine (ACh) release in the BLA and the BLA-projecting cholinergic neurons manifest immediate early gene responses and display increased intrinsic excitability for 2-5 hours following the cue-elicited memory response to the conditioned stimulus. Silencing cue-associated engram-enrolled cholinergic neurons prevents the expression of the defensive response and the subset of cholinergic neurons activated by cue is distinct from those engaged by innate threat. Taken together we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli via the BLA, demonstrating exquisite, functionally refined organization of specific types of memory within the cholinergic basal forebrain.

scholarly journals A functional topography within the cholinergic basal forebrain for processing sensory cues associated with reward and punishment

2021 ◽  
Author(s):  
Blaise Robert ◽  
Eyal Y. Kimchi ◽  
Yurika Watanabe ◽  
Tatenda Chakoma ◽  
Miao Jing ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Regional Differences ◽  
Cholinergic Neurons ◽  
Brain Regions ◽  
Brain State ◽  
Cholinergic Basal Forebrain ◽  
Diagonal Band ◽  
Substantia Innominata ◽  
Feature Processing ◽  
Functional Topography

AbstractBasal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. The basal forebrain features distinct connectivity along its anteroposterior axis that could impart regional differences in feature processing. Here, we simultaneously measured bulk BFCN activity from an anterior structure, the horizontal limb of the diagonal band (HDB), and from the posterior tail of the basal forebrain in globus pallidus and substantia innominata (GP/SI) over a 30-day period as mice learned a sensory reversal task. Although HDB and GP/SI responses were similar for many features, HDB more closely tracked fluctuations in pupil-indexed brain state and exhibited stronger responses to reward omission than to delivery of anticipated awards. In GP/SI, BFCNs were strongly activated by sound, and this response was further enhanced for punishment-predicting – but not reward-predicting – cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.

scholarly journals Nucleus Basalis links sensory stimuli with delayed reinforcement to support learning

2019 ◽  
Author(s):  
W. Guo ◽  
D.B. Polley
Keyword(s):  
Basal Forebrain ◽  
Neural Circuits ◽  
Cortical Plasticity ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Fear Learning ◽  
Delayed Reinforcement ◽  
Sensory Stimuli ◽  
Sensory Inputs ◽  
Cholinergic Basal Forebrain

SummaryLinking stimuli with delayed reinforcement requires neural circuits that can bridge extended temporal gaps. Auditory cortex (ACx) circuits reorganize to support auditory fear learning, but only when afferent sensory inputs temporally overlap with cholinergic reinforcement signals. Here we show that mouse ACx neurons rapidly reorganize to support learning, even when sensory and reinforcement cues are separated by a long gap. We found that cholinergic basal forebrain neurons bypass the temporal delay through multiplexed, short-latency encoding of sensory and reinforcement cues. At the initiation of learning, cholinergic neurons in Nucleus Basalis increase responses to conditioned sound frequencies and increase functional connectivity with ACx. By rapidly scaling up responses to sounds that predict reinforcement, cholinergic inputs jump the gap to align with bottom-up sensory traces and support associative cortical plasticity.

scholarly journals Individual Differences in Interoceptive Accuracy Are Correlated With Salience Network Connectivity in Older Adults

2020 ◽  
Vol 12 ◽  
Author(s):  
Daisuke Ueno ◽  
Teruyuki Matsuoka ◽  
Yuka Kato ◽  
Nobutaka Ayani ◽  
Saaya Maeda ◽  
...  
Keyword(s):  
Older Adults ◽  
Prefrontal Cortex ◽  
Gray Matter Volume ◽  
Region Of Interest ◽  
Insular Cortex ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Salience Network ◽  
Rostral Prefrontal Cortex ◽  
Interoceptive Accuracy

Interoceptive accuracy refers to the ability to consciously perceive the physical condition of the inner body, including one’s heartbeat. In younger adults, interoceptive accuracy is correlated with insular and orbitofrontal cortical connectivity within the salience network (SN). As interoceptive accuracy and insular cortex volume are known to decrease with aging, we aimed to evaluate the correlation between SN connectivity and interoceptive accuracy in older adults. 27 older adults (mean age, 77.29 years, SD = 6.24; 19 female) underwent resting-state functional magnetic resonance imaging, followed by a heartbeat counting task and neuropsychological test. We evaluated the correlation between interoceptive accuracy and SN connectivity with age, sex, cognitive function, and total gray matter volume as covariates. Region of interest-to-region of interest analyses showed that interoceptive accuracy was positively correlated with the functional connectivity (FC) of the left rostral prefrontal cortex with the right insular, right orbitofrontal, and anterior cingulate cortices [F(6,16) = 4.52, false discovery rate (FDR)-corrected p < 0.05]. Moreover, interoceptive accuracy was negatively correlated to the FC of the left anterior insular cortex with right intra-calcarine and visual medial cortices (F(6,16) = 2.04, FDR-corrected p < 0.10). These findings suggest that coordination between systems, with a positive correlation between left rostral prefrontal cortex and the SN and a negative correlation between left insular cortex and vision-related exteroceptive brain regions, is important for maintaining interoceptive accuracy in older adults.

Role of the Basal Forebrain Cholinergic Projection in Somatosensory Cortical Plasticity

1998 ◽  
Vol 79 (6) ◽  
pp. 3216-3228 ◽  
Author(s):  
Robert N. S. Sachdev ◽  
Shao-Ming Lu ◽  
Ron G. Wiley ◽  
Ford F. Ebner
Keyword(s):  
Synaptic Plasticity ◽  
Basal Forebrain ◽  
Cortical Plasticity ◽  
Cortical Cell ◽  
Growth Factor Receptor ◽  
Nucleus Basalis ◽  
Adult Rats ◽  
Cholinergic Basal Forebrain ◽  
Cholinergic Projection

Sachdev, Robert N. S., Shao-Ming Lu, Ron G. Wiley, and Ford F. Ebner. Role of the basal forebrain cholinergic projection in somatosensory cortical plasticity. J. Neurophysiol. 79: 3216–3228, 1998. Trimming all but two whiskers in adult rats produces a predictable change in cortical cell-evoked responses characterized by increased responsiveness to the two intact whiskers and decreased responsiveness to the trimmed whiskers. This type of synaptic plasticity in rat somatic sensory cortex, called “whisker pairing plasticity,” first appears in cells above and below the layer IV barrels. These are also the cortical layers that receive the densest cholinergic inputs from the nucleus basalis. The present study assesses whether the cholinergic inputs to cortex have a role in regulating whisker pairing plasticity. To do this, cholinergic basal forebrain fibers were eliminated using an immunotoxin specific for these fibers. A monoclonal antibody to the low-affinity nerve growth factor receptor 192 IgG, conjugated to the cytotoxin saporin, was injected into cortex to eliminate cholinergic fibers in the barrel field. The immunotoxin reduces acetylcholine esterase (AChE)-positive fibers in S1 cortex by >90% by 3 wk after injection. Sham-depleted animals in which either saporin alone or saporin unconjugated to 192 IgG is injected into the cortex produces no decrease in AChE-positive fibers in cortex. Sham-depleted animals show the expected plasticity in barrel column neurons. In contrast, no plasticity develops in the ACh-depleted, 7-day whisker-paired animals. These results support the conclusion that the basal forebrain cholinergic projection to cortex is an important facilitator of synaptic plasticity in mature cortex.

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