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 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.

Novel Excitatory Actions of Galanin on Rat Cholinergic Basal Forebrain Neurons: Implications for Its Role in Alzheimer's Disease

2002 ◽  
Vol 87 (2) ◽  
pp. 696-704 ◽  
Author(s):  
Jack H. Jhamandas ◽  
Kim H. Harris ◽  
David MacTavish ◽  
Balvinder S. Jassar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Cell Voltage ◽  
Delayed Rectifier ◽  
Cholinergic Basal Forebrain ◽  
Diagonal Band ◽  
Release Of Acetylcholine ◽  
Forebrain Neurons

Galanin, a 29-amino-acid neuropeptide, is generally viewed as an inhibitory neuromodulator in a variety of central systems. Galanin expression is upregulated in the cholinergic basal forebrain nuclei in Alzheimer's disease (AD) and is postulated to play an important role in memory and cognitive function. In this study, application of galanin to acutely dissociated rat neurons from the basal forebrain nucleus diagonal band of Broca (DBB), caused a decrease in whole cell voltage-activated currents in a majority of cells. Galanin reduces a suite of potassium currents, including calcium-activated potassium ( I C), the delayed rectifier ( I K), and transient outward potassium ( I A) conductances, but not calcium or sodium currents. Under current-clamp conditions, application of galanin evoked an increase in excitability and a loss of accommodation in cholinergic DBB neurons. Using single-cell RT-PCR technique, we determined that galanin actions were specific to cholinergic, but not GABAergic DBB neurons The notion that galanin plays a deleterious role in AD is based, in part, on galanin hyperinnervation of cholinergic cells in the basal forebrain of AD patients, its ability to depress acetylcholine release and its inhibitory actions at other CNS sites. However, our results suggest that by virtue of its excitatory actions on cholinergic neurons, galanin may in fact play a compensatory role by augmenting the release of acetylcholine from remaining cholinergic basal forebrain neurons. This action might serve to delay the progression of AD pathology linked to a reduction in central cholinergic tone.

scholarly journals Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

2009 ◽  
Vol 102 (4) ◽  
pp. 2194-2207 ◽  
Author(s):  
David Murchison ◽  
Angelika N. McDermott ◽  
Candi L. LaSarge ◽  
Kathryn A. Peebles ◽  
Jennifer L. Bizon ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Cognitive Status ◽  
Cognitively Impaired ◽  
Aged Rats ◽  
Middle Aged ◽  
Cholinergic Basal Forebrain ◽  
Age Related ◽  
Forebrain Neurons ◽  
Firing Properties

Alterations in neuronal Ca2+ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca2+ influx, buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca2+ current recording with Ca2+-sensitive ratiometric microfluorimetry to measure Ca2+ buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca2+ channel currents. However, Ca2+ buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca2+ buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca2+ buffering by cholinergic basal forebrain neurons may be important during aging.

scholarly journals The diagonal band of broca continually regulates olfactory-mediated behaviors by modulating odor-evoked responses within the olfactory bulb

2020 ◽  
Author(s):  
Inna Schwarz ◽  
Monika Müller ◽  
Irina Pavlova ◽  
Jens Schweihoff ◽  
Fabrizio Musacchio ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Basal Forebrain ◽  
Behavioral Responses ◽  
Brain Regions ◽  
Evoked Responses ◽  
Response Modulation ◽  
Top Down ◽  
Diagonal Band ◽  
Diagonal Band Of Broca ◽  
Interneuron Activity

AbstractSensory perception is modulated in a top-down fashion by higher brain regions to regulate the strength of its own input resulting in the adaptation of behavioral responses. In olfactory perception, the horizontal diagonal band of broca (HDB), embedded in the basal forebrain modulates olfactory information processing by recruiting olfactory bulb (OB) interneuron activity to shape excitatory OB output. Currently, little is known about how specific HDB to OB top down signaling affects complex olfactory-mediated behaviors. Here we show that the olfactory bulb is strongly and differentially innervated by HDB projections. HDB-silencing via tetanus toxin lead to reduced odor-evoked Ca2+-responses in glomeruli of the main OB, underscoring the HDB’s role in odor response modulation. Furthermore, selective, light-mediated silencing of only HDB to OB afferents completely prevented olfactory-mediated habituation and discrimination behaviors. Notably, also social habituation and discrimination behaviors were affected. Here we provide evidence for a novel tri-synaptic paraventricular nucleus (PVN)-HDB-OB axis responsible for modulating these types of behavior. Thus, HDB to OB projections constitute a central top-down pathway for olfactory-mediated habituation and discrimination.

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 Estimation of the Total Number of Cholinergic Neurons Containing Estrogen Receptor-α in the Rat Basal Forebrain

2002 ◽  
Vol 50 (7) ◽  
pp. 891-902 ◽  
Author(s):  
Riitta A. Miettinen ◽  
Giedrius Kalesnykas ◽  
Esa H. Koivisto
Keyword(s):  
Estrogen Receptor ◽  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Estrogen Receptor Α ◽  
Medial Septum ◽  
Nucleus Basalis ◽  
Cell Counting ◽  
Double Immunostaining ◽  
Diagonal Band ◽  
Diagonal Band Of Broca

This study was undertaken to estimate the total number of cholinergic cells and the percentage of cholinergic cells that contain estrogen receptor-α (ERα) in the rat basal forebrain. Double immunostaining for choline acetyltransferase (ChAT) and ERα was carried out on 50-μm-thick free-floating sections. Because routine mounting method causes considerable flattening of the sections, we embedded immunostained sections in Durcupan, an epoxy resin known to cause virtually no shrinkage. When this procedure was used the section thickness was well preserved, individual cells could be clearly identified, and subcellular localization of ERα immunoreactivity was easy to verify. Cell counting in these sections revealed that the rat basal forebrain contains 26,390 ± 1097 (mean ± SEM) cholinergic neurons. This comprises 9674 ± 504 in the medial septum-vertical diagonal band of Broca, 9403 ± 484 in the horizontal diagonal band of Broca, and 7312 ± 281 in the nucleus basalis. In these nuclei, 60%, 46%, and 14% of the cholinergic neurons were colocalized with ERα, respectively. We believe that our results are an improvement on existing data because of the better distinction of individual neurons that the Durcupan embedding method brings.

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.

Sign in / Sign up

Export Citation Format

Share Document