scholarly journals Cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain

2020 ◽  
Author(s):  
Kathryn C. Allaway ◽  
William Muñoz ◽  
Robin Tremblay ◽  
Mia Sherer ◽  
Jacob Herron ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Cholinergic Innervation ◽  
Cholinergic Signaling ◽  
Regional Specificity ◽  
Deep Layers ◽  
Innervation Patterns ◽  
High Degree ◽  
Inside Out ◽  
Cholinergic Projections ◽  
Cholinergic Projection

AbstractThe basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.

scholarly journals Cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kathryn C Allaway ◽  
William Muñoz ◽  
Robin Tremblay ◽  
Mia Sherer ◽  
Jacob Herron ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Cholinergic Innervation ◽  
Cholinergic Signaling ◽  
Mouse Cortex ◽  
Regional Specificity ◽  
Deep Layers ◽  
Innervation Patterns ◽  
High Degree ◽  
Inside Out ◽  
Cholinergic Projection

The basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the mouse cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.

scholarly journals CHANGES IN THE MUCOSA OF THE UTERINE POD IN CANCER OF THE VAGINAL PART AND CERVIX

2020 ◽  
Vol 5 (5) ◽  
pp. 410-435
Author(s):  
M. Mironov
Keyword(s):  
Mucous Membrane ◽  
Individual Case ◽  
The Body ◽  
Lymphoid Cells ◽  
Surface Layers ◽  
First Case ◽  
Epitheloid Cells ◽  
Deep Layers ◽  
High Degree ◽  
Sarcomatous Degeneration

Changes in the mucous membrane of the body of the uterus, accompanying cancer of the vaginal part and cervix, drew special attention after the work of Abel (see No. I), which appeared in 1888. The author studied the mucous membrane of the body of the uterus, taken from extirpated cases of 6 uterus for carcinoma portionis and in 1 case for carcinoma cervicis. "In all cases, the mucous membrane is dull," says the author (p. 279, 1. p.), To a high degree of alteration, while the mucous membrane of the cervix is ​​relatively insignificantly diseased. " These changes, as can be seen from the description of each individual case, concern both the gland and the intermediate tissue, and the first in all cases were multiplied and represented corkscrew gyrus; some of them were enlarged or contained ectases of the lateral walls and processes protruding into the lumen of the gland. Changes in the intermediate tissue in cases 1, 2 and 4 consisted in the multiplication of cells in deep layers, and here they had a short-spindle-shaped shape, small size and went in trains in different directions; in the surface layers, they were more or less round, much larger in size and resembled epitheloid cells. In addition, a nested infiltration with small, round cells (lymphoid cells?) Met in places. In the remaining 4 cases, the changes in the intermediate tissue, according to the author's description, were the same as usually in chronic inflammation (cases 5, 6 and 7) or almost absent (case 3). On the basis of these studies, the author comes to the conclusion that changes in the mucous membrane of the body of the uterus in cancer of the vaginal part and cervix have the character of sarcomatous degeneration, which in observed 1, 2 and 4-m, already reached a rather high degree of 4, in the rest, although it did not appear as sharp as especially in the first case, but nevertheless, these changes, according to the author, cannot be considered as inflammatory, but should be taken only as a more weak degree of the same sarcomatous degeneration, by analogy with the first.

scholarly journals Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaromir Myslivecek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Isolation ◽  
Cholinergic System ◽  
System Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

scholarly journals Optogenetic cholinergic modulation of the mouse superior colliculus in vivo

2015 ◽  
Vol 114 (2) ◽  
pp. 978-988 ◽  
Author(s):  
Elizabeth A. Stubblefield ◽  
John A. Thompson ◽  
Gidon Felsen
Keyword(s):  
Superior Colliculus ◽  
Brain Stem ◽  
Functional Role ◽  
Critical Role ◽  
Pedunculopontine Tegmental Nucleus ◽  
Sensorimotor Transformations ◽  
Deep Layers ◽  
Cholinergic Projection ◽  
Cholinergic Terminals

The superior colliculus (SC) plays a critical role in orienting movements, in part by integrating modulatory influences on the sensorimotor transformations it performs. Many species exhibit a robust brain stem cholinergic projection to the intermediate and deep layers of the SC arising mainly from the pedunculopontine tegmental nucleus (PPTg), which may serve to modulate SC function. However, the physiological effects of this input have not been examined in vivo, preventing an understanding of its functional role. Given the data from slice experiments, cholinergic input may have a net excitatory effect on the SC. Alternatively, the input could have mixed effects, via activation of inhibitory neurons within or upstream of the SC. Distinguishing between these possibilities requires in vivo experiments in which endogenous cholinergic input is directly manipulated. Here we used anatomical and optogenetic techniques to identify and selectively activate brain stem cholinergic terminals entering the intermediate and deep layers of the awake mouse SC and recorded SC neuronal responses. We first quantified the pattern of the cholinergic input to the mouse SC, finding that it was predominantly localized to the intermediate and deep layers. We then found that optogenetic stimulation of cholinergic terminals in the SC significantly increased the activity of a subpopulation of SC neurons. Interestingly, cholinergic input had a broad range of effects on the magnitude and timing of SC responses, perhaps reflecting both monosynaptic and polysynaptic innervation. These findings begin to elucidate the functional role of this cholinergic projection in modulating the processing underlying sensorimotor transformations in the SC.

Protective and anti-inflammatory effects of acetylcholine in the heart

2020 ◽  
Author(s):  
Cibele Rocha-Resende ◽  
Aristobolo Mendes da Silva ◽  
Marco A. M. Prado ◽  
Silvia Guatimosim
Keyword(s):  
Cholinergic System ◽  
Inflammatory Cells ◽  
Cardiac Diseases ◽  
Immune Systems ◽  
Cardiac Inflammation ◽  
Adaptive Immune ◽  
Protective Actions ◽  
Cholinergic Signaling ◽  
Adaptive Immune Systems

The innate and adaptive immune systems play an important role in the development of cardiac diseases. Therefore, it has become critical to identify molecules that can modulate inflammation in the injured heart. In this regard, activation of the cholinergic system in animal models of heart disease has been shown to exert protective actions that include immunomodulation of cardiac inflammation. In this mini-review, we briefly present our current understanding on the cardiac cellular sources of acetylcholine (ACh) (neuronal versus nonneuronal), followed by a discussion on its contribution to the regulation of inflammatory cells. Although the mechanism behind ACh-mediated protection still remains to be fully elucidated, the beneficial immunomodulatory role of the cholinergic signaling emerges as a potential key regulator of cardiac inflammation.

scholarly journals Neuroplasticity in Cholinergic Projections from the Basal Forebrain to the Basolateral Nucleus of the Amygdala in the Kainic Acid Model of Temporal Lobe Epilepsy

2019 ◽  
Vol 20 (22) ◽  
pp. 5688
Author(s):  
Ítalo Rosal Lustosa ◽  
Joana I. Soares ◽  
Giuseppe Biagini ◽  
Nikolai V. Lukoyanov
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Kainic Acid ◽  
Temporal Lobe ◽  
Basal Forebrain ◽  
Cholinergic Innervation ◽  
Vesicular Acetylcholine Transporter ◽  
Adult Rats ◽  
Basolateral Nucleus ◽  
Spontaneous Recurrent Seizures ◽  
Cholinergic Projections

The amygdala is a cerebral region whose function is compromised in temporal lobe epilepsy (TLE). Patients with TLE present cognitive and emotional dysfunctions, of which impairments in recognizing facial expressions have been clearly attributed to amygdala damage. However, damage to the amygdala has been scarcely addressed, with the majority of studies focusing on the hippocampus. The aim of this study was to evaluate epilepsy-related plasticity of cholinergic projections to the basolateral nucleus (BL) of the amygdala. Adult rats received kainic acid (KA) injections and developed status epilepticus. Weeks later, they showed spontaneous recurrent seizures documented by behavioral observations. Changes in cholinergic innervation of the BL were investigated by using an antibody against the vesicular acetylcholine transporter (VAChT). In KA-treated rats, it was found that (i) the BL shrunk to 25% of its original size (p < 0.01 vs. controls, Student’s t-test), (ii) the density of vesicular acetylcholine transporter-immunoreactive (VAChT-IR) varicosities was unchanged, (iii) the volumes of VAChT-IR cell bodies projecting to the BL from the horizontal limb of the diagonal band of Broca, ventral pallidum, and subcommissural part of the substantia innominata were significantly increased (p < 0.05, Bonferroni correction). These results illustrate significant changes in the basal forebrain cholinergic cells projecting to the BL in the presence of spontaneous recurrent seizures.

scholarly journals Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia

2021 ◽  
Author(s):  
Mihai Avram ◽  
Michel J. Grothe ◽  
Lena Meinhold ◽  
Claudia Leucht ◽  
Stefan Leucht ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Cholinergic System ◽  
Structural Integrity ◽  
Specific Effect ◽  
Cholinergic Innervation ◽  
Pathophysiological Mechanism ◽  
Healthy Controls ◽  
Attentional Deficits ◽  
Cognitive Difficulties ◽  
Cholinergic Basal Forebrain

AbstractA potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients’ attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)–based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients’ impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients’ attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN.

Changes in Noradrenergic and Cholinergic Innervation Patterns in the Ovaries in Progesterone-Treated Gilts

2017 ◽  
Vol 156 (1) ◽  
pp. 134
Author(s):  
K.A. Meller ◽  
M. Sobieszczańska ◽  
J. Czarzasta ◽  
B. Jana
Keyword(s):  
Cholinergic Innervation ◽  
Innervation Patterns

scholarly journals Muscarinic Receptor–Dependent Long-Term Depression in Rat Visual Cortex Is PKC Independent but Requires ERK1/2 Activation and Protein Synthesis

2007 ◽  
Vol 98 (4) ◽  
pp. 1862-1870 ◽  
Author(s):  
Portia A. McCoy ◽  
Lori L. McMahon
Keyword(s):  
Protein Synthesis ◽  
Visual Cortex ◽  
Muscarinic Receptor ◽  
Cholinergic System ◽  
Receptor Activation ◽  
Synaptic Function ◽  
Cholinergic Innervation ◽  
Long Term Depression ◽  
M1 Receptor

Intact cholinergic innervation of visual cortex is critical for normal processing of visual information and for spatial memory acquisition and retention. However, a complete description of the mechanisms by which the cholinergic system modifies synaptic function in visual cortex is lacking. Previously it was shown that activation of the m1 subtype of muscarinic receptor induces an activity-dependent and partially N-methyl-d-aspartate receptor (NMDAR)-dependent long-term depression (LTD) at layer 4–layer 2/3 synapses in rat visual cortex slices in vitro. The cellular mechanisms downstream of the Gαq coupled m1 receptor required for induction of this LTD (which we term mLTD) are currently unknown. Here, we confirm a role for m1 receptors in mLTD induction and use a series of pharmacological tools to study the signaling molecules downstream of m1 receptor activation in mLTD induction. We found that mLTD is prevented by inhibitors of L-type Ca2+ channels, the Src kinase family, and the mitogen-activated kinase/extracellular kinase. mLTD is also partially dependent on phospholipase C but is unaffected by blocking protein kinase C. mLTD expression can be long-lasting (>2 h) and its long-term maintenance requires translation. Thus we report the signaling mechanisms underlying induction of an m1 receptor-dependent LTD in visual cortex and the requirement of protein synthesis for long-term expression. This plasticity could be a mechanism by which the cholinergic system modifies glutamatergic synapse function to permit normal visual system processing required for cognition.

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