scholarly journals Reduced Insulin-Like Growth Factor-I Effects in the Basal Forebrain of Aging Mouse

2021 ◽  
Vol 13 ◽  
Author(s):  
Jonathan A. Zegarra-Valdivia ◽  
Irene Chaves-Coira ◽  
Maria Estrella Fernandez de Sevilla ◽  
Laura Martinez-Rachadell ◽  
Julio Esparza ◽  
...  

It is known that aging is frequently accompanied by a decline in cognition. Furthermore, aging is associated with lower serum IGF-I levels that may contribute to this deterioration. We studied the effect of IGF-I in neurons of the horizontal diagonal band of Broca (HDB) of young (≤6 months old) and old (≥20-month-old) mice to determine if changes in the response of these neurons to IGF-I occur along with aging. Local injection of IGF-I in the HDB nucleus increased their neuronal activity and induced fast oscillatory activity in the electrocorticogram (ECoG). Furthermore, IGF-I facilitated tactile responses in the primary somatosensory cortex elicited by air-puffs delivered in the whiskers. These excitatory effects decreased in old mice. Immunohistochemistry showed that cholinergic HDB neurons express IGF-I receptors and that IGF-I injection increased the expression of c-fos in young, but not in old animals. IGF-I increased the activity of optogenetically-identified cholinergic neurons in young animals, suggesting that most of the IGF-I-induced excitatory effects were mediated by activation of these neurons. Effects of aging were partially ameliorated by chronic IGF-I treatment in old mice. The present findings suggest that reduced IGF-I activity in old animals participates in age-associated changes in cortical activity.

2002 ◽  
Vol 50 (7) ◽  
pp. 891-902 ◽  
Author(s):  
Riitta A. Miettinen ◽  
Giedrius Kalesnykas ◽  
Esa H. Koivisto

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.


2021 ◽  
Vol 15 ◽  
Author(s):  
Linghong Chen ◽  
Yuting Ke ◽  
Hong Ma ◽  
Lei Gao ◽  
Yiying Zhou ◽  
...  

The basal forebrain cholinergic system is involved in cognitive processes, but the role of the basal forebrain cholinergic system in depression is unknown. We investigated whether a lesion of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) produces depressive-like behavior and whether fluoxetine or ketamine inhibits such depressive-like behaviors. Here, in rats, we used 192 IgG-saporin to eliminate the cholinergic neurons of the HDB and evaluated depressive-like behaviors using a preference test for sucrose solution and the forced swimming test. Fourteen days after the injection of 192 IgG-saporin into the HDB, the rats exhibited a significantly fewer number of choline acetyltransferase positive cell density in HDB, accompanied with neuronal loss in the entire hippocampus. Meanwhile, these rats significantly reduced preference for sucrose solution, increased immobility time in the forced swimming test, reduced locomotor activity, decreased context dependent memory in fear conditioning and the time spent in the open arms of the plus-maze. A single dose of ketamine (10 mg/kg) increased the sucrose solution consumption, reduced the immobility time in the forced swim test (FST), and increased locomotor activity compared to vehicle-treated rats. Moreover, in rats that were continuously treated with fluoxetine (10 mg/kg/day for 11 days), the sucrose solution consumption increased, the immobility time in the FST decreased, and locomotor activity increased compared to vehicle-treated rats. The present results demonstrate that a lesion of HDB cholinergic neurons results in depressive-like and anxiety-like behaviors and that antidepressants such as fluoxetine or ketamine, can reverse these depressive-like behaviors but not anxiety-like behaviors, and suggest that a lesion of HDB cholinergic neurons and followed hippocampus damage may be involved in the pathogenesis of depression.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Blaise Robert ◽  
Eyal Y Kimchi ◽  
Yurika Watanabe ◽  
Tatenda Chakoma ◽  
Miao Jing ◽  
...  

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.


2019 ◽  
Vol 5 (3) ◽  
pp. eaav1640 ◽  
Author(s):  
Ryan M. Cassidy ◽  
Yungang Lu ◽  
Madhavi Jere ◽  
Jin-Bin Tian ◽  
Yuanzhong Xu ◽  
...  

Animals must consider competing information before deciding to eat: internal signals indicating the desirability of food and external signals indicating the risk involved in eating within a particular environment. The behaviors driven by the former are manifestations of hunger, and the latter, anxiety. The connection between pathologic anxiety and reduced eating in conditions like typical depression and anorexia is well known. Conversely, anti-anxiety drugs such as benzodiazepines increase appetite. Here, we show that GABAergic neurons in the diagonal band of Broca (DBBGABA) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LHGABA). Activation of this circuit reduces anxiety and causes indiscriminate feeding. We also found that diazepam rapidly reduces DBBGABA activity while inducing indiscriminate feeding. Our study reveals that the LHGABA→DBBGABA neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.


1990 ◽  
Vol 38 (4) ◽  
pp. 563-571 ◽  
Author(s):  
G Palacios

Coronal vibratome sections of the rostral part of the medial septum (MS) and vertical limb of the diagonal band of Broca (VDB) nuclei were studied by an immunocytochemical technique using a monoclonal antibody against choline acetyltransferase (ChAT) and a double histochemical method for detection of acid phosphatase (AcPase) and nucleoside diphosphatase (NDPase) activity. The electron microscopic morphology of ChAT-immunoreactive and non-immunoreactive neurons was compared with similar neurons showing both AcPase and NDPase activity. ChAT-labeled and non-labeled neurons were well differentiated by the organization of the endomembrane system and especially by the structure of the rough endoplasmic reticulum (RER) and associated lamellar bodies. These results support the theory that the peculiar ultrastructure of the lamellar bodies in each neuron is related to the pattern of organization of the endomembrane system and its function. The significance of the lamellar bodies is discussed, and the data of the present work, together with findings described by other investigators. These data suggest that these bodies are predominant in efferent projection neurons in the basal forebrain nuclei.


1999 ◽  
Vol 276 (6) ◽  
pp. R1766-R1771
Author(s):  
Gilbert J. Kirouac ◽  
Quentin J. Pittman

Previous investigations suggest a possible role in cardiovascular regulation for neurons of the mediobasal forebrain. The present study was designed to determine the location and morphology of basal forebrain neurons that respond to acute changes in arterial blood pressure. Extracellular recordings of single units were done in α-chloralose- or urethan-anesthetized rats. The effect of cardiovascular pressor (phenylephrine, 1–2 μg/kg iv) and depressor (sodium nitroprusside, 0.5–1 μg/kg iv) events on the discharge rates of units was determined. Some of the neurons tested were subsequently filled with biocytin using the juxtacellular method. Brain sections were processed using the avidin-biotin complex reaction to reveal a Golgi-like appearance of the neuron. Of 32 neurons located in the horizontal limb of the diagonal band of Broca (hDB), 13 (41%) were found to be excited by depressor events. Barosensitive biocytin-labeled cells were located in all regions of the hDB and had small- to medium-sized cell bodies with sparse and simple dendritic morphology. Only 2 of 47 neurons tested in the region of the olfactory tubercle, islands of Calleja (IC), and ventral pallidum responded to changes in arterial blood pressure. The results of the present investigation suggest a role in the regulation of cardiovascular function for neurons of the hDB. The findings also suggest that most neurons in the olfactory tubercle, including the IC complex, do not respond to acute changes in arterial blood pressure.


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