scholarly journals Cerebellar connectivity maps embody individual adaptive behavior

2021 ◽  
Author(s):  
Ludovic Spaeth ◽  
Jyotika Bahuguna ◽  
Theo Gagneux ◽  
Kevin Dorgans ◽  
Izumi Sugihara ◽  
...  
Keyword(s):  
Critical Period ◽  
Spatial Organization ◽  
Granule Cells ◽  
Functional Organization ◽  
Motor Adaptation ◽  
Synaptic Connectivity ◽  
General Motor ◽  
Behavioral Features ◽  
Specific Manner ◽  
Context Specific

AbstractFrom planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral features of mice locomotion, suggesting that GC-PC networks encode a general motor context as well as individual specific internal models underlying motor adaptation.

scholarly journals Tonotopic and non-auditory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Aaron Benson Wong ◽  
J Gerard G Borst
Keyword(s):  
Inferior Colliculus ◽  
Spatial Organization ◽  
Functional Organization ◽  
Frequency Tuning ◽  
Gabaergic Neurons ◽  
Two Photon ◽  
Spontaneous Movements ◽  
Multimodal Information ◽  
Auditory Organization

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal responses, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust, double rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.

scholarly journals KLF4 Induces Mesenchymal–Epithelial Transition (MET) by Suppressing Multiple EMT-Inducing Transcription Factors

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5135
Author(s):  
Ayalur Raghu Subbalakshmi ◽  
Sarthak Sahoo ◽  
Isabelle McMullen ◽  
Aaditya Narayan Saxena ◽  
Sudhanva Kalasapura Venugopal ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Patient Survival ◽  
Dynamic Processes ◽  
State Transitions ◽  
Specific Manner ◽  
Context Specific ◽  
Phenotypic Shift ◽  
Acting In Concert ◽  
Epithelial State ◽  
Mesenchymal Epithelial Transition

Epithelial–Mesenchymal Plasticity (EMP) refers to reversible dynamic processes where cells can transition from epithelial to mesenchymal (EMT) or from mesenchymal to epithelial (MET) phenotypes. Both these processes are modulated by multiple transcription factors acting in concert. While EMT-inducing transcription factors (TFs)—TWIST1/2, ZEB1/2, SNAIL1/2/3, GSC, and FOXC2—are well-characterized, the MET-inducing TFs are relatively poorly understood (OVOL1/2 and GRHL1/2). Here, using mechanism-based mathematical modeling, we show that transcription factor KLF4 can delay the onset of EMT by suppressing multiple EMT-TFs. Our simulations suggest that KLF4 overexpression can promote a phenotypic shift toward a more epithelial state, an observation suggested by the negative correlation of KLF4 with EMT-TFs and with transcriptomic-based EMT scoring metrics in cancer cell lines. We also show that the influence of KLF4 in modulating the EMT dynamics can be strengthened by its ability to inhibit cell-state transitions at the epigenetic level. Thus, KLF4 can inhibit EMT through multiple parallel paths and can act as a putative MET-TF. KLF4 associates with the patient survival metrics across multiple cancers in a context-specific manner, highlighting the complex association of EMP with patient survival.

scholarly journals A connectivity-constrained computational account of topographic organization in high-level visual cortex

2021 ◽  
Author(s):  
Nicholas M Blauch ◽  
Marlene Behrmann ◽  
David Plaut
Keyword(s):  
Visual Processing ◽  
Spatial Organization ◽  
Functional Organization ◽  
Spatial Clusters ◽  
Feature Extracting ◽  
Domain Specific ◽  
Visual Processes ◽  
Topographic Organization ◽  
High Level ◽  
Multiple Domain

Inferotemporal cortex (IT) in humans and other primates is topographically organized, with multiple domain-selective areas and other general patterns of functional organization. What factors underlie this organization, and what can this neural arrangement tell us about the mechanisms of high level vision? Here, we present an account of topographic organization involving a computational model with two components: 1) a feature-extracting encoder model of early visual processes, followed by 2) a model of high-level hierarchical visual processing in IT subject to specific biological constraints. In particular, minimizing the wiring cost on spatially organized feedforward and lateral connections within IT, combined with constraining the feedforward processing to be strictly excitatory, results in a hierarchical, topographic organization. This organization replicates a number of key properties of primate IT cortex, including the presence of domain-selective spatial clusters preferentially involved in the representation of faces, objects, and scenes, within-domain topographic organization such as animacy and indoor/outdoor distinctions, and generic spatial organization whereby the response correlation of pairs of units falls off with their distance. The model supports a view in which both domain-specific and domain-general topographic organization arise in the visual system from an optimization process that maximizes behavioral performance while minimizing wiring costs.

Feedforward Inhibition Controls the Spread of Granule Cell–Induced Purkinje Cell Activity in the Cerebellar Cortex

2007 ◽  
Vol 97 (1) ◽  
pp. 248-263 ◽  
Author(s):  
Fidel Santamaria ◽  
Patrick G. Tripp ◽  
James M. Bower
Keyword(s):  
Cerebellar Cortex ◽  
Granule Cells ◽  
Functional Organization ◽  
Cerebellar Granule Cells ◽  
Molecular Layer ◽  
Cell Activity ◽  
Excitatory Input ◽  
Cortical Inhibition ◽  
Before And After

Synapses associated with the parallel fiber (pf) axons of cerebellar granule cells constitute the largest excitatory input onto Purkinje cells (PCs). Although most theories of cerebellar function assume these synapses produce an excitatory sequential “beamlike” activation of PCs, numerous physiological studies have failed to find such beams. Using a computer model of the cerebellar cortex we predicted that the lack of PCs beams is explained by the concomitant pf activation of feedforward molecular layer inhibition. This prediction was tested, in vivo, by recording PCs sharing a common set of pfs before and after pharmacologically blocking inhibitory inputs. As predicted by the model, pf-induced beams of excitatory PC responses were seen only when inhibition was blocked. Blocking inhibition did not have a significant effect in the excitability of the cerebellar cortex. We conclude that pfs work in concert with feedforward cortical inhibition to regulate the excitability of the PC dendrite without directly influencing PC spiking output. This conclusion requires a significant reassessment of classical interpretations of the functional organization of the cerebellar cortex.

Functional Organization of Squirrel Monkey Primary Auditory Cortex: Responses to Pure Tones

2001 ◽  
Vol 85 (4) ◽  
pp. 1732-1749 ◽  
Author(s):  
Steven W. Cheung ◽  
Purvis H. Bedenbaugh ◽  
Srikantan S. Nagarajan ◽  
Christoph E. Schreiner
Keyword(s):  
Receptive Field ◽  
Auditory Cortex ◽  
Squirrel Monkey ◽  
Spatial Organization ◽  
Functional Organization ◽  
Primary Auditory Cortex ◽  
Complex Sound ◽  
Sound Coding ◽  
Field Gradients ◽  
Pure Tones

The spatial organization of response parameters in squirrel monkey primary auditory cortex (AI) accessible on the temporal gyrus was determined with the excitatory receptive field to pure tone stimuli. Dense, microelectrode mapping of the temporal gyrus in four animals revealed that characteristic frequency (CF) had a smooth, monotonic gradient that systematically changed from lower values (0.5 kHz) in the caudoventral quadrant to higher values (5–6 kHz) in the rostrodorsal quadrant. The extent of AI on the temporal gyrus was ∼4 mm in the rostrocaudal axis and 2–3 mm in the dorsoventral axis. The entire length of isofrequency contours below 6 kHz was accessible for study. Several independent, spatially organized functional response parameters were demonstrated for the squirrel monkey AI. Latency, the asymptotic minimum arrival time for spikes with increasing sound pressure levels at CF, was topographically organized as a monotonic gradient across AI nearly orthogonal to the CF gradient. Rostral AI had longer latencies (range = 4 ms). Threshold and bandwidth co-varied with the CF. Factoring out the contribution of the CF on threshold variance, residual threshold showed a monotonic gradient across AI that had higher values (range = 10 dB) caudally. The orientation of the threshold gradient was significantly different from the CF gradient. CF-corrected bandwidth, residual Q10, was spatially organized in local patches of coherent values whose loci were specific for each monkey. These data support the existence of multiple, overlying receptive field gradients within AI and form the basis to develop a conceptual framework to understand simple and complex sound coding in mammals.

scholarly journals A Late Critical Period for Frequency Modulated Sweeps in the Mouse Auditory System

2019 ◽  
Vol 30 (4) ◽  
pp. 2586-2599 ◽  
Author(s):  
Stitipragyan Bhumika ◽  
Mari Nakamura ◽  
Patricia Valerio ◽  
Magdalena Solyga ◽  
Henrik Lindén ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Auditory System ◽  
Critical Period ◽  
Noise Exposure ◽  
Functional Organization ◽  
Time Windows ◽  
Immunohistochemical Analysis ◽  
Critical Periods ◽  
Complex Sounds

Abstract Neuronal circuits are shaped by experience during time windows of increased plasticity in postnatal development. In the auditory system, the critical period for the simplest sounds—pure frequency tones—is well defined. Critical periods for more complex sounds remain to be elucidated. We used in vivo electrophysiological recordings in the mouse auditory cortex to demonstrate that passive exposure to frequency modulated sweeps (FMS) from postnatal day 31 to 38 leads to long-term changes in the temporal representation of sweep directions. Immunohistochemical analysis revealed a decreased percentage of layer 4 parvalbumin-positive (PV+) cells during this critical period, paralleled with a transient increase in responses to FMS, but not to pure tones. Preventing the PV+ cell decrease with continuous white noise exposure delayed the critical period onset, suggesting a reduction in inhibition as a mechanism for this plasticity. Our findings shed new light on the dependence of plastic windows on stimulus complexity that persistently sculpt the functional organization of the auditory cortex.

Co-ordinate high level expression of the murine α- and β-globin genes is regulated in a context-specific manner by erythroid Krüppel-like factor (EKLF)

2007 ◽  
Vol 38 (2) ◽  
pp. 134 ◽  
Author(s):  
John M. Cunningham ◽  
Valerie Jansen ◽  
Shaji Ramachandran ◽  
Aurelie Desgardin ◽  
Jin He ◽  
...  
Keyword(s):  
Globin Genes ◽  
High Level Expression ◽  
Specific Manner ◽  
Context Specific ◽  
High Level

scholarly journals Lumican Exhibits Anti-Angiogenic Activity in a Context Specific Manner

2013 ◽  
Vol 6 (3) ◽  
pp. 263-271 ◽  
Author(s):  
Bikram Sharma ◽  
Megan D. Ramus ◽  
Christopher T. Kirkwood ◽  
Emma E. Sperry ◽  
Pao-Hsien Chu ◽  
...  
Keyword(s):  
Angiogenic Activity ◽  
Specific Manner ◽  
Context Specific

scholarly journals Observation of others’ threat reactions recovers memories previously shaped by firsthand experiences

2021 ◽  
Vol 118 (30) ◽  
pp. e2101290118
Author(s):  
Jan Haaker ◽  
Lorenzo Diaz-Mataix ◽  
Gemma Guillazo-Blanch ◽  
Sara A. Stark ◽  
Lea Kern ◽  
...  
Keyword(s):  
Defensive Behavior ◽  
Physiological Responses ◽  
Associative Memories ◽  
Specific Manner ◽  
Analogous Experiment ◽  
Human Participants ◽  
Context Specific ◽  
Conditioned Cues

Information about dangers can spread effectively by observation of others’ threat responses. Yet, it is unclear if such observational threat information interacts with associative memories that are shaped by the individual’s direct, firsthand experiences. Here, we show in humans and rats that the mere observation of a conspecific’s threat reactions reinstates previously learned and extinguished threat responses in the observer. In two experiments, human participants displayed elevated physiological responses to threat-conditioned cues after observational reinstatement in a context-specific manner. The elevation of physiological responses (arousal) was further specific to the context that was observed as dangerous. An analogous experiment in rats provided converging results by demonstrating reinstatement of defensive behavior after observing another rat’s threat reactions. Taken together, our findings provide cross-species evidence that observation of others’ threat reactions can recover associations previously shaped by direct, firsthand aversive experiences. Our study offers a perspective on how retrieval of threat memories draws from associative mechanisms that might underlie both observations of others’ and firsthand experiences.

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