scholarly journals The influence of the corticothalamic projection on responses in thalamus and cortex

2002 ◽  
Vol 357 (1428) ◽  
pp. 1823-1834 ◽  
Author(s):  
Florentin Wörgötter ◽  
Dirk Eyding ◽  
Jeffrey D. Macklis ◽  
Klaus Funke

We review results on the in vivo properties of neurons in the dorsal lateral geniculate nucleus (dLGN) that receives its afferent input from the retina and projects to the visual cortex. In addition, the dLGN receives input from the brain stem and from a rather strong corticothalamic back–projection, which originates in layer 6 of the visual cortex. We compare the behaviour of dLGN cells during spontaneous changes of the frequency contents of the electroencephalograph (EEG) (which are mainly related to a changing brain stem influence), with those that are obtained when experimentally silencing the corticothalamic feedback. The spatial and temporal response properties of dLGN cells are compared during these two conditions, and we report that the neurons behave similarly during a synchronized EEG state and during inactive corticothalamic feedback. In both situations, dLGN cells are rather phasic and their remaining tonic activity is temporally dispersed, indicating a hyperpolarizing effect. By means of a novel method, we were able to chronically eliminate a large proportion of the corticothalamic projection neurons from the otherwise intact cortex. In this condition, we found that cortical cells also lose their EEG specific response differences but, in this instance, probably due to a facilitatory (depolarizing) plasticity reaction of the remaining network.

1983 ◽  
Vol 49 (3) ◽  
pp. 804-818 ◽  
Author(s):  
D. G. Tieman ◽  
M. A. McCall ◽  
H. V. Hirsch

1. In order to investigate the effects of an imbalance in stimulation to the eyes without the confounding influence of continuous deprivation of one eye, we reared cats with unequal alternating monocular exposure (AME) and, for comparison, cats with equal AME. We recorded extracellularly from single cells in area 17 of visual cortex. 2. For unequal AME cats, a majority of the cells that were visually responsive were dominated by the eye that had received more patterned visual experience. The percentage of cells dominated by the more experienced eye was greater with a large imbalance in stimulation to the two eyes (AME 8/1, 77%) than with a small imbalance (AME 8/4, 62%). 3. For both equal AME cats and unequal AME cats, we obtained evidence for differences in cells activated by the contralateral and by the ipsilateral afferents. a) In equal AME cats receiving only 1 h of exposure per day, we obtained a greater dominance by the contralateral eye (60%) than in equal AME cats receiving 8 h of exposure per day (42%). b) Although a large imbalance in stimulation (AME 8/1) resulted in a shift in ocular dominance in both cortical hemispheres, a moderate imbalance (AME 8/4) resulted in a smaller shift, which was apparent only in the hemisphere ipsilateral to the less-experienced eye. 4. The percentage of cortical cells responsive to each eye was uniform throughout the depth of cortex. Thus, for the unequal AME cats, cells activated by the less-experienced eye were no more frequent in layer IV of visual cortex than in the infragranular and supragranular layers. 5. Although almost all cells recorded from AME cats had relatively normal receptive-field properties, three receptive-field properties of cells in unequal AME cats showed an effect of the rearing. In each case cells dominated by the less-experienced eye and recorded in the cortical hemisphere ipsilateral to it showed the largest changes. These cells a) were more poorly tuned, b) had lower cutoff velocities, and c) had smaller receptive fields. 6. It is suggested that cortical cells that putatively receive Y-cell afferents from the dorsal lateral geniculate nucleus (LGNd) are more affected by an imbalance in stimulation than are cortical cells that putatively receive X-cell afferents. Thus, the decrease in mean receptive-field area and cutoff velocity for the cells dominated by the less-experienced eye is suggested to be due to a greater shift in ocular dominance by the cortical cells receiving Y-cell afferents from the LGNd. 7. The interaction between binocular competition and deprivation of pattern vision may contribute to differences between monocularly deprived cats and unequal AME cats.


1979 ◽  
Vol 42 (6) ◽  
pp. 1692-1710 ◽  
Author(s):  
G. G. Blasdel ◽  
J. D. Pettigrew

1. The importance of synchronous activation in maintaining cortical binocularity was studied physiologically in kittens that had been reared under different regimens of alternating monocular deprivation. 2. Three different techniques were employed to provide alternate monocular stimulation: a) mechanical shutters placed before the animals' eyes; b) goggles fitted with complementary colored cutoff filters, which restricted visual input to one eye at a time; and c) two rotating gratings that were 90 degrees out of phase. In the third technique, the gratings were always orthogonal to one another and viewed separately through cutoff filters. This allowed us to exploit the orientation selectivity of cortical cells and thereby stimulate them alternately through each eye without simultaneously affecting activity in the dorsal lateral geniculate nucleus (dLGN). 3. We based our conclusions on a sample of 691 neurons, which we recorded in 21 animals. Results with all techniques were remarkably consistent. Binocular cortical inputs predominated at normal or nearly normal levels, even when a number of seconds elapsed between successive exposures of each eye. 4. An interonset interval of at least 10 s was required to make a substantial reduction in binocularity. This interval can be separated into two parts--the duration of exclusive monocular stimulation and the time when neither channel receives input. Of these, the latter appeared to be less important. Blanking times of 0.15--1.0 s did not affect binocularity if the interonset interval was 1 or 10 s; and in one experiment where the blanking time was 9 s, the resulting disruption in binocularity was less than that found with shorter blanking times and the same interonset interval. 5. Our results imply that mechanisms responsible for the disappearance of binocular cortical inputs require independent stimulation of each eye for periods of at least a few seconds; this stimulation must be of a kind that is known to excite cortical cells. Our results with the rotating grafting show, in addition, that the mechanisms whose timing we have measured are intrinsic to the cortex.


2020 ◽  
Author(s):  
Kenta M Hagihara ◽  
Ayako Wendy Ishikawa ◽  
Yumiko Yoshimura ◽  
Yoshiaki Tagawa ◽  
Kenichi Ohki

Abstract Integration of information processed separately in distributed brain regions is essential for brain functions. This integration is enabled by long-range projection neurons, and further, concerted interactions between long-range projections and local microcircuits are crucial. It is not well known, however, how this interaction is implemented in cortical circuits. Here, to decipher this logic, using callosal projection neurons (CPNs) in layer 2/3 of the mouse visual cortex as a model of long-range projections, we found that CPNs exhibited distinct response properties and fine-scale local connectivity patterns. In vivo 2-photon calcium imaging revealed that CPNs showed a higher ipsilateral (to their somata) eye preference, and that CPN pairs showed stronger signal/noise correlation than random pairs. Slice recordings showed CPNs were preferentially connected to CPNs, demonstrating the existence of projection target-dependent fine-scale subnetworks. Collectively, our results suggest that long-range projection target predicts response properties and local connectivity of cortical projection neurons.


2018 ◽  
Vol 119 (3) ◽  
pp. 771-785
Author(s):  
Alison Boxwell ◽  
David Terman ◽  
Marion Frank ◽  
Yuchio Yanagawa ◽  
Joseph B. Travers

Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, because rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole cell patch-clamp recordings of inhibitory and noninhibitory neurons in a mouse expressing Venus under the control of the VGAT promoter. We then used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison with in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated 1) increasing numbers of convergent afferents (2–10) result in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, 2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared with convergence of randomly selected afferent input, and 3) inhibition narrowed the BOT to more realistically model the in vivo rNST data. NEW & NOTEWORTHY Using a combination of in vivo and in vitro neurophysiology together with conductance-based modeling, we show how patterns of convergence and inhibition interact in the rostral (gustatory) solitary nucleus to maintain signal fidelity. Although increasing convergence led to a systematic increase in firing frequency, tuning specificity was maintained with a pattern of afferent inputs sharing the best-stimulus compared with random inputs. Tonic inhibition further enhanced response fidelity.


2001 ◽  
Vol 13 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Ulrich Hillenbrand ◽  
J. Leo van Hemmen

The thalamus is the major gate to the cortex, and its contribution to cortical receptive field properties is well established. Cortical feedback to the thalamus is, in turn, the anatomically dominant input to relay cells, yet its influence on thalamic processing has been difficult to interpret. For an understanding of complex sensory processing, detailed concepts of the corticothalamic interplay need to be established. To study corticogeniculate processing in a model, we draw on various physiological and anatomical data concerning the intrinsic dynamics of geniculate relay neurons, the cortical influence on relay modes, lagged and nonlagged neurons, and the structure of visual cortical receptive fields. In extensive computer simulations, we elaborate the novel hypothesis that the visual cortex controls via feedback the temporal response properties of geniculate relay cells in a way that alters the tuning of cortical cells for speed.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2396
Author(s):  
Nina Schoenwaelder ◽  
Inken Salewski ◽  
Nadja Engel ◽  
Mareike Krause ◽  
Björn Schneider ◽  
...  

Cyclin-dependent kinase inhibitors (CDKi´s) display cytotoxic activity against different malignancies, including head and neck squamous cell carcinomas (HNSCC). By coordinating the DNA damage response, these substances may be combined with cytostatics to enhance cytotoxicity. Here, we investigated the influence of different CDKi´s (palbociclib, dinaciclib, THZ1) on two HNSCC cell lines in monotherapy and combination therapy with clinically-approved drugs (5-FU, Cisplatin, cetuximab). Apoptosis/necrosis, cell cycle, invasiveness, senescence, radiation-induced γ-H2AX DNA double-strand breaks, and effects on the actin filament were studied. Furthermore, the potential to increase tumor immunogenicity was assessed by analyzing Calreticulin translocation and immune relevant surface markers. Finally, an in vivo mouse model was used to analyze the effect of dinaciclib and Cisplatin combination therapy. Dinaciclib, palbociclib, and THZ1 displayed anti-neoplastic activity after low-dose treatment, while the two latter substances slightly enhanced radiosensitivity. Dinaciclib decelerated wound healing, decreased invasiveness, and induced MHC-I, accompanied by high amounts of surface-bound Calreticulin. Numbers of early and late apoptotic cells increased initially (24 h), while necrosis dominated afterward. Antitumoral effects of the selective CDKi palbociclib were weaker, but combinations with 5-FU potentiated effects of the monotherapy. Additionally, CDKi and CDKi/chemotherapy combinations induced MHC I, indicative of enhanced immunogenicity. The in vivo studies revealed a cell line-specific response with best tumor growth control in the combination approach. Global acting CDKi’s should be further investigated as targeting agents for HNSCC, either individually or in combination with selected drugs. The ability of dinaciclib to increase the immunogenicity of tumor cells renders this substance a particularly interesting candidate for immune-based oncological treatment regimens.


Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1465-1475 ◽  
Author(s):  
T Kozlova ◽  
G V Pokholkova ◽  
G Tzertzinis ◽  
J D Sutherland ◽  
I F Zhimulev ◽  
...  

Abstract DHR38 is a member of the steroid receptor superfamily in Drosophila homologous to the vertebrate NGFI-B-type orphan receptors. In addition to binding to specific response elements as a monomer, DHR38 interacts with the USP component of the ecdysone receptor complex in vitro, in yeast and in a cell line, suggesting that DHR38 might modulate ecdysone-triggered signals in the fly. We characterized the molecular structure and expression of the Dhr38 gene and initiated an in vivo analysis of its function(s) in development. The Dhr38 transcription unit spans more than 40 kb in length, includes four introns, and produces at least four mRNA isoforms differentially expressed in development; two of these are greatly enriched in the pupal stage and encode nested polypeptides. We characterized four alleles of Dhr38: a P-element enchancer trap line, l(2)02306, which shows exclusively epidermal staining in the late larval, pre-pupal and pupal stages, and three EMS-induced alleles. Dhr38 alleles cause localized fragility and rupturing of the adult cuticle, demonstrating that Dhr38 plays an important role in late stages of epidermal metamorphosis.


Author(s):  
Xiaolian Li ◽  
Qi Zhu ◽  
Wim Vanduffel

AbstractThe visuotopic organization of dorsal visual cortex rostral to area V2 in primates has been a longstanding source of controversy. Using sub-millimeter phase-encoded retinotopic fMRI mapping, we recently provided evidence for a surprisingly similar visuotopic organization in dorsal visual cortex of macaques compared to previously published maps in New world monkeys (Zhu and Vanduffel, Proc Natl Acad Sci USA 116:2306–2311, 2019). Although individual quadrant representations could be robustly delineated in that study, their grouping into hemifield representations remains a major challenge. Here, we combined in-vivo high-resolution myelin density mapping based on MR imaging (400 µm isotropic resolution) with fine-grained retinotopic fMRI to quantitatively compare myelin densities across retinotopically defined visual areas in macaques. Complementing previously documented differences in populational receptive-field (pRF) size and visual field signs, myelin densities of both quadrants of the dorsolateral posterior area (DLP) and area V3A are significantly different compared to dorsal and ventral area V3. Moreover, no differences in myelin density were observed between the two matching quadrants belonging to areas DLP, V3A, V1, V2 and V4, respectively. This was not the case, however, for the dorsal and ventral quadrants of area V3, which showed significant differences in MR-defined myelin densities, corroborating evidence of previous myelin staining studies. Interestingly, the pRF sizes and visual field signs of both quadrant representations in V3 are not different. Although myelin density correlates with curvature and anticorrelates with cortical thickness when measured across the entire cortex, exactly as in humans, the myelin density results in the visual areas cannot be explained by variability in cortical thickness and curvature between these areas. The present myelin density results largely support our previous model to group the two quadrants of DLP and V3A, rather than grouping DLP- with V3v into a single area VLP, or V3d with V3A+ into DM.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Caitlin Siu ◽  
Justin Balsor ◽  
Sam Merlin ◽  
Frederick Federer ◽  
Alessandra Angelucci

AbstractThe mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area-specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.


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