Abstract:Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated r… Show more
“…There was a significant main effect of sex ( F
(1, 66) = 12.232, p = 0.001) and a significant main effect of age ( F
(2, 66) = 39.717, p < 0.001), indicating differences among pre-puberty, adult, and old animals. Post hoc analysis showed significant differences among all age groups (Table 1), consistent with our previous findings [19, 20]. Fig.…”
Section: Resultssupporting
confidence: 92%
“…Spontaneous network activity was assessed by means of local field potential (LFP) recordings (sampled at 5 or 10 kHz, band-passed filtered at 1–3000 Hz)––obtained from cortical layers 2/3 (electrodes were always placed in the middle of layers 2/3) using low impedance (~0.5 MΩ) glass pipettes filled with aCSF. As shown in our previous analysis using simultaneous LFP and intracellular recordings under identical methodology, this type of LFP events correspond to intracellularly defined Up states [19, 20]. Signals were acquired and amplified (MultiClamp 700B, Axon Instruments), digitized (Instrutech, ITC-18), and viewed on-line with appropriate software (Axograph X, version 1.3.5).…”
BackgroundSeveral molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex.MethodsUp state activity was monitored by local field potential recordings in coronal brain slices of male and female mice across three ages with distinct secretion profiles of sex hormones: (i) pre-puberty (17–21 days old), (ii) 3–9 adult (months old), and (iii) old (19–24 months old).ResultsFemale mice of all ages exhibited longer and more frequent Up states compared to aged-matched male mice. Power spectrum analysis revealed sex differences in the relative power of Up state events, with female mice showing reduced power in the delta range (1–4 Hz) and increased power in the theta range (4–8 Hz) compared to male mice. No sex differences were found in the characteristics of Up state peak voltage and latency.ConclusionsThe present study revealed for the first time sex differences in intracortical network activity, using an ex vivo paradigm of spontaneously occurring Up/Down states. We report significant sex differences in Up state properties that are already present in pre-puberty animals and are maintained through adulthood and old age.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-017-0143-9) contains supplementary material, which is available to authorized users.
“…There was a significant main effect of sex ( F
(1, 66) = 12.232, p = 0.001) and a significant main effect of age ( F
(2, 66) = 39.717, p < 0.001), indicating differences among pre-puberty, adult, and old animals. Post hoc analysis showed significant differences among all age groups (Table 1), consistent with our previous findings [19, 20]. Fig.…”
Section: Resultssupporting
confidence: 92%
“…Spontaneous network activity was assessed by means of local field potential (LFP) recordings (sampled at 5 or 10 kHz, band-passed filtered at 1–3000 Hz)––obtained from cortical layers 2/3 (electrodes were always placed in the middle of layers 2/3) using low impedance (~0.5 MΩ) glass pipettes filled with aCSF. As shown in our previous analysis using simultaneous LFP and intracellular recordings under identical methodology, this type of LFP events correspond to intracellularly defined Up states [19, 20]. Signals were acquired and amplified (MultiClamp 700B, Axon Instruments), digitized (Instrutech, ITC-18), and viewed on-line with appropriate software (Axograph X, version 1.3.5).…”
BackgroundSeveral molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex.MethodsUp state activity was monitored by local field potential recordings in coronal brain slices of male and female mice across three ages with distinct secretion profiles of sex hormones: (i) pre-puberty (17–21 days old), (ii) 3–9 adult (months old), and (iii) old (19–24 months old).ResultsFemale mice of all ages exhibited longer and more frequent Up states compared to aged-matched male mice. Power spectrum analysis revealed sex differences in the relative power of Up state events, with female mice showing reduced power in the delta range (1–4 Hz) and increased power in the theta range (4–8 Hz) compared to male mice. No sex differences were found in the characteristics of Up state peak voltage and latency.ConclusionsThe present study revealed for the first time sex differences in intracortical network activity, using an ex vivo paradigm of spontaneously occurring Up/Down states. We report significant sex differences in Up state properties that are already present in pre-puberty animals and are maintained through adulthood and old age.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-017-0143-9) contains supplementary material, which is available to authorized users.
“…3a). This is compatible with experimental data showing the existence of spontaneous persistent cortical activity for stages mostly after the second postnatal week 3,21,24 and their absence during early development 7,21 . In our model, in the absence of a stimulus, these FPs emerge mainly because of the developmental increase and decrease in background activity 2,3,7 and membrane resistance 2,10 , respectively.…”
Section: Resultssupporting
confidence: 92%
“…In the following, we will call this specific FP the rest state of the network. This analysis result fits well with experimental findings of near-zero hertz spontaneous activity of immature populations 3,20 , and the absence of spontaneous network’s persistent activity states mainly during periods of physiological blindness 7,21 .…”
During neocortical development, network activity undergoes a dramatic transition from largely synchronized, so-called cluster activity, to a relatively sparse pattern around the time of eye-opening in rodents. Biophysical mechanisms underlying this sparsification phenomenon remain poorly understood. Here, we present a dynamic systems modeling study of a developing neural network that provides the first mechanistic insights into sparsification. We find that the rest state of immature networks is strongly affected by the dynamics of a transient, unstable state hidden in their firing activities, allowing these networks to either be silent or generate large cluster activity. We address how, and which, specific developmental changes in neuronal and synaptic parameters drive sparsification. We also reveal how these changes refine the information processing capabilities of an in vivo developing network, mainly by showing a developmental reduction in the instability of network’s firing activity, an effective availability of inhibition-stabilized states, and an emergence of spontaneous attractors and state transition mechanisms. Furthermore, we demonstrate the key role of GABAergic transmission and depressing glutamatergic synapses in governing the spatiotemporal evolution of cluster activity. These results, by providing a strong link between experimental observations and model behavior, suggest how adult sparse coding networks may emerge developmentally.
“…3A-B). The upward shape of UP states in our recordings, as compared to the biphasic shape of UP states in previous studies (32,37,38), is primarily due to the difference in the resistance (tip size) of the recording electrode used (~1 MΩ in our recordings vs. ~0.5 MΩ in previous recordings (37,38)), as shown in Fig. S2B.…”
Section: Elongated Spontaneously Occurring Cortical Up States In Astrcontrasting
Fragile X syndrome (FXS) is one of the most common inherited intellectual disability (ID) disorders, in which the loss of FMRP protein induces a range of cellular signaling changes primarily through excess protein synthesis. Although neuron-centered molecular and cellular events underlying FXS have been characterized, how different CNS cell types are involved in typical FXS synaptic signaling changes and behavioral phenotypes is largely unknown. Recent evidence suggests that selective loss of astroglial FMRP is able to dysregulate glutamate uptake, increase spine density, and impair motor-skill learning. Here we investigated the effect of astroglial FMRP on synaptic signaling and FXS-related behavioral and learning phenotypes in astroglial Fmr1 cKO and cON mice in which FMRP expression is selectively diminished or restored in astroglia. We found that selective loss of astroglial FMRP contributes to cortical hyperexcitability by enhancing NMDAR-mediated evoked but not spontaneous miniEPSCs and elongating cortical UP state duration. Selective loss of astroglial FMRP is also sufficient to increase locomotor hyperactivity, significantly diminish social novelty preference, and induce memory acquisition and extinction deficits in astroglial Fmr1 cKO mice. Importantly, re-expression of astroglial FMRP is able to significantly rescue the hyperactivity (evoked NMDAR response, UP state duration, and open field test) and social novelty preference in astroglial Fmr1 cON mice. These results demonstrate a profound role of astroglial FMRP in the evoked synaptic signaling, spontaneously occurring cortical UP states, and FXS-related behavioral and learning phenotypes and provide important new insights in the cell type consideration for the FMRP reactivation strategy.
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