Local Connections to Specific Types of Layer 6 Neurons in the Rat Visual Cortex

2006 ◽  
Vol 95 (3) ◽  
pp. 1751-1761 ◽  
Author(s):  
Amir Zarrinpar ◽  
Edward M. Callaway

Because layer 6 of the cerebral cortex receives direct thalamic input and provides projections back to the thalamus, it is in a unique position to influence thalamocortical interactions. Different types of layer 6 pyramidal neurons provide output to different thalamic nuclei, and it is therefore of interest to understand the sources of functional input to these neurons. We studied the morphologies and local excitatory input to individual layer 6 neurons in rat visual cortex by combining intracellular labeling and recording with laser-scanning photostimulation. As in previous photostimulation studies, we found significant differences in the sources of local excitatory input to different cell types. Most notably, there were differences in local input to neurons that, based on analogy to barrel cortex, are likely to project only to the lateral geniculate nucleus of the thalamus versus those that are likely to also project to the lateral posterior nucleus. The more striking finding, however, was the paucity of superficial layer input to layer 6 neurons in the rat visual cortex, contrasting sharply with layer 6 neurons in the primate visual cortex. These observations provide insight into differences in function between cortical projections to first-order versus higher-order thalamic nuclei and also show that these circuits can be organized differently in different species.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
B Semihcan Sermet ◽  
Pavel Truschow ◽  
Michael Feyerabend ◽  
Johannes M Mayrhofer ◽  
Tess B Oram ◽  
...  

Mouse primary somatosensory barrel cortex (wS1) processes whisker sensory information, receiving input from two distinct thalamic nuclei. The first-order ventral posterior medial (VPM) somatosensory thalamic nucleus most densely innervates layer 4 (L4) barrels, whereas the higher-order posterior thalamic nucleus (medial part, POm) most densely innervates L1 and L5A. We optogenetically stimulated VPM or POm axons, and recorded evoked excitatory postsynaptic potentials (EPSPs) in different cell-types across cortical layers in wS1. We found that excitatory neurons and parvalbumin-expressing inhibitory neurons received the largest EPSPs, dominated by VPM input to L4 and POm input to L5A. In contrast, somatostatin-expressing inhibitory neurons received very little input from either pathway in any layer. Vasoactive intestinal peptide-expressing inhibitory neurons received an intermediate level of excitatory input with less apparent layer-specificity. Our data help understand how wS1 neocortical microcircuits might process and integrate sensory and higher-order inputs.


2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Alicja Kreczko ◽  
Anubhuthi Goel ◽  
Lihua Song ◽  
Hey-Kyoung Lee

Proper functioning of the visual system depends on maturation of both excitatory and inhibitory synapses within the visual cortex. Considering that perisomatic inhibition is one of the key factors that control the critical period in visual cortex, it is pertinent to understand its regulation by visual experience. To do this, we developed an immunohistochemical method that allows three-dimensional (3D) analysis of the glutamic acid decarboxylase (GAD) 65-positive inhibitory terminals in the visual cortex. Using this method on transgenic mice expressing yellow fluorescence protein (YFP) in a subset of neurons, we found that the number of somatic GAD65-puncta on individual layer 2/3 pyramidal neurons is reduced when mice are dark-reared from birth and reverted to normal levels by re-exposure to light. There was no change in GAD65-puncta volume or intensity. These results support the reorganization of inhibitory circuitry within layer 2/3 of visual cortex in response to changes in visual experience.


2011 ◽  
Vol 106 (5) ◽  
pp. 2499-2505 ◽  
Author(s):  
Emily Petrus ◽  
Terence T. Anguh ◽  
Huy Pho ◽  
Angela Lee ◽  
Nicholas Gammon ◽  
...  

Layer 6 (L6) of primary sensory cortices is distinct from other layers in that it provides a major cortical input to primary sensory thalamic nuclei. L6 pyramidal neurons in the primary visual cortex (V1) send projections to the lateral geniculate nucleus (LGN), as well as to the thalamic reticular nucleus and higher order thalamic nuclei. Although L6 neurons are proposed to modulate the activity of thalamic relay neurons, how sensory experience regulates L6 neurons is largely unknown. Several days of visual deprivation homeostatically adjusts excitatory synapses in L4 and L2/3 of V1 depending on the developmental age. For instance, L4 exhibits an early critical period during which visual deprivation homeostatically scales up excitatory synaptic transmission. On the other hand, homeostatic changes in L2/3 excitatory synapses are delayed and persist into adulthood. In the present study we examined how visual deprivation affects excitatory synapses on L6 pyramidal neurons. We found that L6 pyramidal neurons homeostatically increase the strength of excitatory synapses following 2 days of dark exposure (DE), which was readily reversed by 1 day of light exposure. This effect was restricted to an early critical period, similar to that reported for L4 neurons. However, at a later developmental age, a longer duration of DE (1 wk) decreased the strength of excitatory synapses, which reversed to normal levels with light exposure. These changes are opposite to what is predicted from the homeostatic plasticity theory. Our results suggest that L6 neurons differentially adjust their excitatory synaptic strength to visual deprivation depending on the age of the animals.


1997 ◽  
Vol 14 (2) ◽  
pp. 241-251 ◽  
Author(s):  
Anne K. Wiser ◽  
Edward M. Callaway

AbstractTo study the relationship between ocular dominance columns (ODCs) and axonal projections of individual layer 6 pyramidal neurons in the primary visual cortex, neurons were intracellularly labeled with biocytin in live slices prepared from macaque monkeys that had received an intravitreal injection of tetrodotoxin (TTX). The TTX injection indirectly causes a decrease in cytochrome oxidase (CO) expression in the cortical ODCs corresponding to the treated eye (Wong-Riley & Carroll, 1984). Sections from slices with labeled layer 6 neurons were double stained for biocytin and CO, to allow visualization of neuronal processes as well as ODCs. Twenty-seven layer 6 pyramidal neurons in ODC-labeled slices were analyzed. These neurons were classified according to the criteria of Wiser and Callaway (1996). Eight of these are class I neurons, which have dense axonal projections to the monocular layer 4C. The remaining 19 are class II neurons which project primarily to the binocular layers outside 4C. Among class I neurons, two have dense axonal arbors in layer 4Cα (type Iα), one in layer 4Cβ (type Iβ), and two throughout the depth of layer 4C (type IC). None of these neurons have ODC-specific axonal arbors. The remaining three class I neurons have focused axonal projections in layers 4Cβ and 4A (type IβA). All three appear to have axonal arbors predominantly within their home ODC in layer 4C. The axonal arbors of class II neurons do not appear to relate to ODCs in any specific fashion.


2015 ◽  
Vol 112 (45) ◽  
pp. 14072-14077 ◽  
Author(s):  
Robert Egger ◽  
Arno C. Schmitt ◽  
Damian J. Wallace ◽  
Bert Sakmann ◽  
Marcel Oberlaender ◽  
...  

Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2–5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism—consistent with the theory of distal dendritic shunting—that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency.


2020 ◽  
Author(s):  
Rahel Kastli ◽  
Rasmus Vighagen ◽  
Alexander van der Bourg ◽  
Ali Ozgur Argunsah ◽  
Asim Iqbal ◽  
...  

AbstractTwo inhibitory cell types involved in modulating barrel cortex activity and perception during active whisking in adult mice, are the VIP+ and SST+ interneurons. Here we identify a developmental transition point of structural and functional rearrangements onto these interneuron types around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ at both time points. In addition, we also uncover that whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rahel Kastli ◽  
Rasmus Vighagen ◽  
Alexander van der Bourg ◽  
Ali Özgür Argunsah ◽  
Asim Iqbal ◽  
...  

AbstractVasocative-intestinal-peptide (VIP+) and somatostatin (SST+) interneurons are involved in modulating barrel cortex activity and perception during active whisking. Here we identify a developmental transition point of structural and functional rearrangements onto these interneurons around the start of active sensation at P14. Using in vivo two-photon Ca2+ imaging, we find that before P14, both interneuron types respond stronger to a multi-whisker stimulus, whereas after P14 their responses diverge, with VIP+ cells losing their multi-whisker preference and SST+ neurons enhancing theirs. Additionally, we find that Ca2+ signaling dynamics increase in precision as the cells and network mature. Rabies virus tracings followed by tissue clearing, as well as photostimulation-coupled electrophysiology reveal that SST+ cells receive higher cross-barrel inputs compared to VIP+ neurons at both time points. In addition, whereas prior to P14 both cell types receive direct input from the sensory thalamus, after P14 VIP+ cells show reduced inputs and SST+ cells largely shift to motor-related thalamic nuclei.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bastiaan van der Veen ◽  
Sampath K. T. Kapanaiah ◽  
Kasyoka Kilonzo ◽  
Peter Steele-Perkins ◽  
Martin M. Jendryka ◽  
...  

AbstractPathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rongkang Deng ◽  
Joseph P. Y. Kao ◽  
Patrick O. Kanold

AbstractThe development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.


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