Acetylcholinesterase and Neural Development: New Tricks for an Old Dog?

Physiology ◽  
1993 ◽  
Vol 8 (6) ◽  
pp. 266-272 ◽  
Author(s):  
RT Robertson ◽  
J Yu

Patterns of intense acetylcholinesterase activity occur transiently in developing thalamocortical projection neurons and their terminal fields in sensory regions of cerebral cortex. These patterns correlate well with the time of ingrowth of thalamocortical axons and synaptogenesis with cortical neurons.

1982 ◽  
Vol 48 (4) ◽  
pp. 1048-1057 ◽  
Author(s):  
H. Asanuma ◽  
R. S. Waters ◽  
H. Yumiya

1. The corticocortical projection from area 3a to area 4 gamma was restudied using tranquilized cats. 2. Intracortical microstimulation (ICMS) of a given locus in area 3a produced effects on neurons in area 4 gamma that were located in a small area extending along the direction of the radial fibers constituting a columnar shape. 3. Cortical neurons in area 3a that projected to a particular neuron in area 4 gamma were located in a region that extended along the direction of the radial fibers and constituted a columnar shape. 4. Two-thirds of the projection neurons in area 3a had different receptive fields from those of neurons in the projected area in 4 gamma, thus suggesting that the 3a neurons are not simply transferring peripheral information to the 4 gamma neurons. 5. ICMS delivered to area 3a rarely excited 4 gamma neurons but rather facilitated their evoked discharges. 6. It is suggested that the activity of corticocortical projection from area 3a to 4 gamma can influence the activity of 4 gamma neurons only when combined with other inputs to the motor cortex.


1994 ◽  
Vol 72 (5) ◽  
pp. 2438-2450 ◽  
Author(s):  
R. W. Rhoades ◽  
C. A. Bennett-Clarke ◽  
M. Y. Shi ◽  
R. D. Mooney

1. Recent immunocytochemical and receptor binding data have demonstrated a transient somatotopic patterning of serotonin (5-HT)-immunoreactive fibers in the primary somatosensory cortex of developing rats and a transient expression of 5-HT1B receptors on thalamocortical axons from the ventral posteromedial thalamic nucleus (VPM). 2. These results suggest that 5-HT should strongly modulate thalamocortical synaptic transmission for a limited time during postnatal development. This hypothesis was tested in intracellular recording experiments carried out in thalamocortical slice preparations that included VPM, the thalamic radiations, and the primary somatosensory cortex. Effects of 5-HT and analogues were monitored on membrane potentials and input resistances of cortical neurons and on the amplitude of the synaptic potentials evoked in them by stimulation of VPM. 3. Results obtained from cortical neurons in slices taken from rats during the first 2 wk of life indicated that 5-HT strongly inhibited the VPM-evoked excitatory postsynaptic potential (EPSP) recorded from cortical neurons in a dose-dependent manner. In contrast, 5-HT had no significant effects on membrane potential, input resistance, or depolarizations induced by direct application of glutamic acid to cortical cells. 4. The effects of 5-HT were mimicked by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline maleate and antagonized by the 5-HT1B receptor antagonist (-)-pindolol. The 5-HT1A agonist [(+/-)8-hydroxydipropylaminotetralin HBr] (8-OH-DPAT) had less effect on the VPM-elicited EPSP, and the effects of 5-HT upon this response were generally not antagonized by either 1-(2-methoxyphenyl)-4-[4-(2- phthalimmido)butyl]piperazine HBr (a 5-HT1A antagonist) or ketanserine (a 5-HT2 antagonist) or spiperone (a 5-HT1A and 2 antagonist). 5. The ability of 5-HT to inhibit the VPM-evoked EPSP in cortical neurons was significantly reduced in slices from animals > 2 wk of age. The effectiveness of TFMPP in such animals was even more attenuated than that of 5-HT, and the effectiveness of 8-OH-DPAT was unchanged with age. These results are consistent with the disappearance of 5-HT1B receptors from thalamocortical axons after the second postnatal week and the maintenance of 5-HT1A receptors on some neurons. 6. All of the results obtained in this study are consistent with the conclusion that 5-HT has a profound, but developmentally transient, presynaptic inhibitory effect upon thalamocortical transmission in the rat's somatosensory cortex.


2020 ◽  
Author(s):  
Ziheng Zhou ◽  
Shuguang Wang ◽  
Dengwei Zhang ◽  
Xiaosen Jiang ◽  
Jie Li ◽  
...  

AbstractBackgroundThe specification and differentiation of neocortical projection neurons is a complex process under precise molecular regulation; however, little is known about the similarities and differences in cerebral cortex development between human and mouse at single-cell resolution.ResultsHere, using single-cell RNA-seq (scRNA-seq) data we explore the divergence and conservation of human and mouse cerebral cortex development using 18,446 and 7,610 neocortical cells. Systematic cross-species comparison reveals that the overall transcriptome profile in human cerebral cortex is similar to that in mouse such as cell types and their markers genes. By single-cell trajectories analysis we find human and mouse excitatory neurons have different developmental trajectories of neocortical projection neurons, ligand-receptor interactions and gene expression patterns. Further analysis reveals a refinement of neuron differentiation that occurred in human but not in mouse, suggesting that excitatory neurons in human undergo refined transcriptional states in later development stage. By contrast, for glial cells and inhibitory neurons we detected conserved developmental trajectories in human and mouse.ConclusionsTaken together, our study integrates scRNA-seq data of cerebral cortex development in human and mouse, and uncovers distinct developing models in neocortical projection neurons. The earlier activation of cognition -related genes in human may explain the differences in behavior, learning or memory abilities between the two species.


2002 ◽  
Vol 87 (4) ◽  
pp. 2113-2123 ◽  
Author(s):  
K.-P. Hoffmann ◽  
F. Bremmer ◽  
A. Thiele ◽  
C. Distler

The cortical projection to the subcortical pathway underlying the optokinetic reflex was studied using antidromic electrical stimulation in the midbrain structures nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) while simultaneously recording from cortical neurons in the superior temporal sulcus (STS) of macaque monkeys. Projection neurons were found in all subregions of the middle temporal area (MT) as well as in the medial superior temporal area (MST). Antidromic latencies ranged from 0.9 to 6 ms with a median of 1.8 ms. There was a strong bias in the population of cortical neurons projecting to the NOT-DTN for ipsiversive stimulus movement (towards the recording side), whereas in the population of cortical neurons not projecting to the NOT-DTN a more or less equal distribution of stimulus directions was evident. Our data indicate that there is no special area in the posterior STS coding for ipsiversive horizontal stimulus movement. Instead, a specific selection of cortical neurons from areas MT and MST forms the projection to the NOT-DTN and as a subpopulation has the same directional bias as their subcortical target neurons. These findings are discussed in relation to the functional grouping of cortical output as an organizational principle for specific motor responses.


2020 ◽  
Vol 76 (1) ◽  
pp. 23-31
Author(s):  
Jinsu Park ◽  
Meenu Madan ◽  
Srinivasulu Chigurupati ◽  
Seung Hyun Baek ◽  
Yoonsuk Cho ◽  
...  

Abstract The accumulation of amyloid-β (Aβ) is a characteristic event in the pathogenesis of Alzheimer’s disease (AD). Aquaporin 1 (AQP1) is a membrane water channel protein belonging to the AQP family. AQP1 levels are elevated in the cerebral cortex during the early stages of AD, but the role of AQP1 in AD pathogenesis is unclear. We first determined the expression and distribution of AQP1 in brain tissue samples of AD patients and two AD mouse models (3xTg-AD and 5xFAD). AQP1 accumulation was observed in vulnerable neurons in the cerebral cortex of AD patients, and in neurons affected by the Aβ or tau pathology in the 3xTg-AD and 5xFAD mice. AQP1 levels increased in neurons as aging progressed in the AD mouse models. Stress stimuli increased AQP1 in primary cortical neurons. In response to cellular stress, AQP1 appeared to translocate to endocytic compartments of β- and γ-secretase activities. Ectopic expression of AQP1 in human neuroblastoma cells overexpressing amyloid precussir protein (APP) with the Swedish mutations reduced β-secretase (BACE1)-mediated cleavage of APP and reduced Aβ production without altering the nonamyloidogenic pathway. Conversely, knockdown of AQP1 enhanced BACE1 activity and Aβ production. Immunoprecipitation experiments showed that AQP1 decreased the association of BACE1 with APP. Analysis of a human database showed that the amount of Aβ decreases as the expression of AQP1 increases. These results suggest that the upregulation of AQP1 is an adaptive response of neurons to stress that reduces Aβ production by inhibiting the binding between BACE1 and APP.


1991 ◽  
Vol 65 (4) ◽  
pp. 841-859 ◽  
Author(s):  
Y. M. Chino ◽  
E. L. Smith ◽  
H. Wada ◽  
W. H. Ridder ◽  
A. L. Langston ◽  
...  

1. Extracellular single-cell recording techniques were employed to investigate the effects of ocular misalignment on the postnatal development of the spatial response properties of striate cortical neurons. The primary objective of the study was to gain insight into the neural basis of strabismic amblyopia. 2. Two basic rearing strategies were used to study specific aspects of experimental strabismus in developing kittens. In one group, strabismus was optically induced by fitting kittens with goggles that held a 15-diopter base-in prism in front of one eye (MP) or both eyes (BP) between the ages of 4 wk and 4 mo. In the second group, a unilateral esotropia was surgically induced at 3 wks of age either by the simple resection of the lateral rectus muscle tendon (tenotomy) or by a more drastic procedure that involved removing sections of the lateral rectus and superior oblique muscles (myectomy). In addition, the eyelids of the nondeviating eyes of these kittens were sutured closed (ESO/MD). The first rearing paradigm isolated the effects of conflicting visual inputs on neural development, whereas the second procedure isolated the effects of anomalous ocular motility by producing a misalignment without putting the deviated eye at a competitive disadvantage. 3. The recording experiments were conducted when the animals were greater than or equal to 9 mo of age. A total of 445 striate cortical neurons were isolated and quantitatively studied in 17 cats (3 MPs, 3 BPs, 5 ESO/MDs, 3 goggle-reared controls, and 3 normals). In addition, we analyzed the distribution of preferred stimulus orientations of 1,205 single units that had been studied qualitatively in our previous investigation of 42 kittens reared with optically induced strabismus. 4. As expected, the proportion of binocularly driven units was reduced in both MP and BP cats. The great majority of units in ESO/MD animals were exclusively driven or highly dominated by the open deviating eye. 5. Prism-reared animals showed physiological deficits in spatial resolution, contrast sensitivity, contrast gain, and peak firing rate. These effects were manifest in both eyes, although there was always an interocular asymmetry in the deficits observed in the two eyes. In MP animals, the units dominated by the treated eye, which was contralateral to the recording hemisphere, were on the average more severely affected. The interocular asymmetry was smaller in BP cats; however, two of the three BP animals also showed a greater deficit in those units dominated by the contralateral eye.(ABSTRACT TRUNCATED AT 400 WORDS)


2016 ◽  
Vol 291 (33) ◽  
pp. 17369-17381 ◽  
Author(s):  
Jin-jing Yao ◽  
Qian-Ru Zhao ◽  
Dong-Dong Liu ◽  
Chi-Wing Chow ◽  
Yan-Ai Mei

Neuritin is an important neurotrophin that regulates neural development, synaptic plasticity, and neuronal survival. Elucidating the downstream molecular signaling is important for potential therapeutic applications of neuritin in neuronal dysfunctions. We previously showed that neuritin up-regulates transient potassium outward current (IA) subunit Kv4.2 expression and increases IA densities, in part by activating the insulin receptor signaling pathway. Molecular mechanisms of neuritin-induced Kv4.2 expression remain elusive. Here, we report that the Ca2+/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons. We found that neuritin elevates intracellular Ca2+ and increases Kv4.2 expression and IA densities; this effect was sensitive to CaN inhibition and was eliminated in Nfatc4−/− mice but not in Nfatc2−/− mice. Stimulation with neuritin significantly increased nuclear accumulation of NFATc4 in cerebellum granule cells and HeLa cells, which expressed IR. Furthermore, NFATc4 was recruited to the Kv4.2 gene promoter loci detected by luciferase reporter and chromatin immunoprecipitation assays. More importantly, data obtained from cortical neurons following adeno-associated virus-mediated overexpression of neuritin indicated that reduced neuronal excitability and increased formation of dendritic spines were abrogated in the Nfatc4−/− mice. Together, these data demonstrate an indispensable role for the CaN/NFATc4 signaling pathway in neuritin-regulated neuronal functions.


Sign in / Sign up

Export Citation Format

Share Document