The emergence of functional microcircuits in visual cortex

Ko, Ho; Cossell, Lee; Baragli, Chiara; Antolík, Ján; Clopath, Claudia; Hofer, Sonja B.; Mrsic-Flogel, Thomas D.

doi:10.1038/nature12015

Cited by 407 publications

(552 citation statements)

References 47 publications

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“…The linear RF describes the relative position of ON (response to light increments) and OFF (response to light decrements) subfields in visual space, and thus provides information about visual features to which a neuron is most sensitive, including their orientation, phase, spatial frequency and size. RFs of nearby cortical neurons were highly diverse within each imaged population in L2/3 [12][13][14][15] (example region in Fig. 2b).…”

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confidence: 99%

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Functional organization of excitatory synaptic strength in primary visual cortex

Cossell

Iacaruso

Muir

et al. 2015

Nature

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The strength of synaptic connections fundamentally determines how neurons influence each other's firing. Excitatory connection amplitudes between pairs of cortical neurons vary over two orders of magnitude, comprising only very few strong connections among many weaker ones [1][2][3][4][5][6][7][8][9] . Although this highly skewed distribution of connection strengths is observed in diverse cortical areas 1-9 , its functional significance remains unknown: it is not clear how connection strength relates to neuronal response properties, nor how strong and weak inputs contribute to information processing in local microcircuits. Here we reveal that the strength of connections between layer 2/3 (L2/3) pyramidal neurons in mouse primary visual cortex (V1) obeys a simple rule-the few strong connections occur between neurons with most correlated responses, while only weak connections link neurons with uncorrelated responses. Moreover, we show that strong and reciprocal connections occur between cells with similar spatial receptive field structure. Although weak connections far outnumber strong connections, each neuron receives the majority of its local excitation from a small number of strong inputs provided by the few neurons with similar responses to visual features. By dominating recurrent excitation, these infrequent yet powerful inputs disproportionately contribute to feature preference and selectivity. Therefore, our results show that the apparently complex organization of excitatory connection strength reflects the Reprints and permissions information is available at www.nature.com/reprints.

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confidence: 99%

“…The fact that there are only very few strong connections in neocortical circuits reflects the low number of cell pairs with highly correlated responses. Therefore, the strength of synaptic coupling mirrors the strength of functional coupling, a relationship which may arise from correlation-based learning rules 15,24 .…”

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confidence: 99%

Functional organization of excitatory synaptic strength in primary visual cortex

Cossell

Iacaruso

Muir

et al. 2015

Nature

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519

670

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“…Although functional electrical coupling between excitatory neurons was only detected from the late embryonic stages to the first postnatal week (7,10,11), accumulated evidence indicates that CX26 proteins are present in excitatory neurons throughout neocortical development (13,15,16). To determine whether CX26 proteins in excitatory neurons, after the period of electrical coupling, modulate synaptic transmission, we deleted CX26 from excitatory neurons after the first postnatal week (late cKO, Fig.…”

Section: Deletion Of Cx26 During the Period Of Active Electrical Coupmentioning

confidence: 99%

“…Electrical couplings are the morphological correlates of dye coupling and low resistance intercellular pathways (9). Functional electrical coupling between excitatory neurons has been abundantly observed at late embryonic and early postnatal stages (10,11). As electrical synapses approach the time point of their elimination, chemical connections between excitatory neurons begin to emerge, illustrating a sequential developmental time course for the two types of connections among excitatory neurons (6,11).…”

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Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

Chen

Liu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior. Conditional deletion of Connexin 26 (CX26) in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces spontaneous firing activity and the frequency and size of spontaneous network oscillations at postnatal day 5-6. Moreover, CX26-conditional knockout (CX26-cKO) neurons tend to have simpler dendritic trees and lower spine density compared with wild-type neurons. Importantly, early, but not late, postnatal deletion of CX26, decreases the frequency of miniature excitatory postsynaptic currents (mEPSCs) in both young and adult mice, whereas miniature inhibitory postsynaptic currents (mIPSCs) were unaffected. Furthermore, CX26-cKO mice exhibit increased anxiety-related behavior. These results suggest that electrical coupling between excitatory neurons at early postnatal stages is a critical step for neocortical development and function.CX26 | development | anxiety | neocortex D uring neocortical development, gap junction-mediated electrical coupling plays a critical role in various developmental processes, including neuronal migration (1, 2), synaptogenesis (3), and synchronous firing (4, 5). It is generally believed that gap junction-mediated communication between excitatory neurons during development is required for the formation of chemical synapses (6). For example, we previously showed that sister excitatory neurons in the neocortex are initially electrically coupled, and blockade of this electrotonic communication impairs the subsequent formation of specific chemical synapses between them in ontogenetic neuronal clones (7), as well as the functional similarity (8). Whereas these studies have provided crucial insights into the role of gap junctions in the precise microcircuit assembly of excitatory neurons and functional organization of the neocortex, whether electrical coupling-mediated networks contribute to the overall development of the neocortex and animal behavior remains largely unknown.Electrical coupling networks among excitatory neurons in the neocortex are developmentally regulated. Electrical couplings are the morphological correlates of dye coupling and low resistance intercellular pathways (9). Functional electrical coupling between excitatory neurons has been abundantly observed at late embryonic and early postnatal stages (10, 11). As electrical synapses approach the time point of their elimination, chemical connections between excitatory neurons begin to emerge, illustrating a sequential developmental time course for the two types of connect...

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“…However, the visual system must also appropriately wire up circuits to support the emergence of many basic receptive field (RF) properties, including orientation selectivity (OS), direction selectivity (DS), spatial frequency (SF) preference, and linearity. Thus far, only a handful of studies have quantified the early maturation of a subset of these properties in mouse V1 (Fagiolini et al, 2003;Rochefort et al, 2011;Wang et al, , 2013Ko et al, 2013Ko et al, , 2014. No single study has systematically quantified the simultaneous development of these RF properties in the awake mouse as a function of cortical layer in monocular V1.…”

Section: Introductionmentioning

confidence: 99%

Layer-Specific Refinement of Visual Cortex Function after Eye Opening in the Awake Mouse

2015

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The laminar structure and conserved cellular organization of mouse visual cortex provide a useful model to determine the mechanisms underlying the development of visual system function. However, the normal development of many receptive field properties has not yet been thoroughly quantified, particularly with respect to layer identity and in the absence of anesthesia. Here, we use multisite electrophysiological recording in the awake mouse across an extended period of development, starting at eye opening, to measure receptive field properties and behavioral-state modulation of responsiveness. We find selective responses for orientation, direction, and spatial frequency at eye opening, which are similar across cortical layers. After this initial similarity, we observe layer-specific maturation of orientation selectivity, direction selectivity, and linearity over the following week. Developmental increases in selectivity are most robust and similar between layers 2-4, whereas layers 5 and 6 undergo distinct refinement patterns. Finally, we studied layer-specific behavioral-state modulation of cortical activity and observed a striking reorganization in the effects of running on response gain. During week 1 after eye opening, running increases responsiveness in layers 4 and 5, whereas in adulthood, the effects of running are most pronounced in layer 2/3. Together, these data demonstrate that response selectivity is present in all layers of the primary visual cortex (V1) at eye opening in the awake mouse and identify the features of basic V1 function that are further shaped over this early developmental period in a layer-specific manner.

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The emergence of functional microcircuits in visual cortex

Cited by 407 publications

References 47 publications

Functional organization of excitatory synaptic strength in primary visual cortex

Functional organization of excitatory synaptic strength in primary visual cortex

Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

Layer-Specific Refinement of Visual Cortex Function after Eye Opening in the Awake Mouse

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