A gradual depth-dependent change in connectivity features of supragranular pyramidal cells in rat barrel cortex

Abstract Subcortical band heterotopia (SBH), also known as double-cortex syndrome, is a neuronal migration disorder characterized by an accumulation of neurons in a heterotopic band below the normotopic cortex. The majority of patients with SBH have mild to moderate intellectual disability and intractable epilepsy. However, it is still not clear how cortical networks are organized in SBH patients and how this abnormal organization contributes to improper brain function. In this study, cortical networks were investigated in the barrel cortex in an animal model of SBH induced by in utero knockdown of Dcx, main causative gene of this condition in human patients. When the SBH was localized below the Barrel Field (BF), layer (L) four projection to correctly positioned L2/3 pyramidal cells was weakened due to lower connectivity. Conversely, when the SBH was below an adjacent cortical region, the excitatory L4 to L2/3 projection was stronger due to increased L4 neuron excitability, synaptic strength and excitation/inhibition ratio of L4 to L2/3 connection. We propose that these developmental alterations contribute to the spectrum of clinical dysfunctions reported in patients with SBH.

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Serotonergic Modulation of Spontaneous and Evoked Transmitter Release in Layer II Pyramidal Cells of Rat Somatosensory Cortex

Cerebral Cortex ◽

10.1093/cercor/bhaa285 ◽

2020 ◽

Author(s):

Fransiscus Adrian Agahari ◽

Christian Stricker

Keyword(s):

Somatosensory Cortex ◽

Transmitter Release ◽

Barrel Cortex ◽

Signal To Noise Ratio ◽

Pyramidal Cells ◽

Mepsc Frequency ◽

Spontaneous Noise ◽

Synaptic Dynamics ◽

Rat Somatosensory Cortex ◽

Almost All

Abstract As axons from the raphe nuclei densely innervate the somatosensory cortex, we investigated how serotonin (5-HT) modulates transmitter release in layer II pyramidal cells of rat barrel cortex. In the presence of tetrodotoxin and gabazine, 10 μM 5-HT caused a waxing and waning in the frequency of miniature excitatory postsynaptic currents (mEPSC) with no effect on amplitude. Specifically, within 15 min of recording the mEPSC frequency initially increased by 28 ± 7%, then dropped to below control (−15 ± 3%), before resurging back to 27 ± 7% larger than control. These changes were seen in 47% of pyramidal cells (responders) and were mediated by 5-HT2C receptors (5-HT2CR). Waxing resulted from phospholipase C activation, IP3 production, and Ca2+ release from presynaptic stores. Waning was prevented if PKC was blocked. In contrast, in paired recordings, the unitary EPSC amplitude was reduced by 50 ± 3% after 5-HT exposure in almost all cases with no significant effect on paired-pulse ratio and synaptic dynamics. This sustained EPSC reduction was also caused by 5-HT2R, but was mediated by presynaptic Gβγ subunits likely limiting influx through CaV2 channels. EPSC reduction, together with enhanced spontaneous noise in a restricted subset of inputs, could temporarily diminish the signal-to-noise ratio and affect the computation in the neocortical microcircuit.

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Development of Intrinsic Properties and Excitability of Layer 2/3 Pyramidal Neurons During a Critical Period for Sensory Maps in Rat Barrel Cortex

Journal of Neurophysiology ◽

10.1152/jn.00598.2003 ◽

2004 ◽

Vol 92 (1) ◽

pp. 144-156 ◽

Cited By ~ 53

Author(s):

Miguel Maravall ◽

Edward A. Stern ◽

Karel Svoboda

Keyword(s):

Critical Period ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Pyramidal Cells ◽

Membrane Properties ◽

Sensory Maps ◽

Layer 2 ◽

Whole Cell Recordings ◽

Passive Membrane Properties

The development of layer 2/3 sensory maps in rat barrel cortex (BC) is experience dependent with a critical period around postnatal days (PND) 10–14. The role of intrinsic response properties of neurons in this plasticity has not been investigated. Here we characterize the development of BC layer 2/3 intrinsic responses to identify possible sites of plasticity. Whole cell recordings were performed on pyramidal cells in acute BC slices from control and deprived rats, over ages spanning the critical period (PND 12, 14, and 17). Vibrissa trimming began at PND 9. Spiking behavior changed from phasic (more spike frequency adaptation) to regular (less adaptation) with age, such that the number of action potentials per stimulus increased. Changes in spiking properties were related to the strength of a slow Ca2+-dependent afterhyperpolarization. Maturation of the spiking properties of layer 2/3 pyramidal neurons coincided with the close of the critical period and was delayed by deprivation. Other measures of excitability, including I-f curves and passive membrane properties, were affected by development but unaffected by whisker deprivation.

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Morphological Characteristics of Electrophysiologically Characterized Layer Vb Pyramidal Cells in Rat Barrel Cortex

PLoS ONE ◽

10.1371/journal.pone.0164004 ◽

2016 ◽

Vol 11 (10) ◽

pp. e0164004 ◽

Cited By ~ 4

Author(s):

Jochen F. Staiger ◽

Alexandre J. C. Loucif ◽

Dirk Schubert ◽

Martin Möck

Keyword(s):

Barrel Cortex ◽

Morphological Characteristics ◽

Pyramidal Cells

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Layer-Specific Intracolumnar and Transcolumnar Functional Connectivity of Layer V Pyramidal Cells in Rat Barrel Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.21-10-03580.2001 ◽

2001 ◽

Vol 21 (10) ◽

pp. 3580-3592 ◽

Cited By ~ 142

Author(s):

Dirk Schubert ◽

Jochen F. Staiger ◽

Nichole Cho ◽

Rolf Kötter ◽

Karl Zilles ◽

...

Keyword(s):

Functional Connectivity ◽

Barrel Cortex ◽

Pyramidal Cells ◽

Layer V

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Layer 6A pyramidal cells subtypes form synaptic microcircuits with distinct functional and structural properties

10.1101/2021.01.13.426506 ◽

2021 ◽

Author(s):

Danqing Yang ◽

Guanxiao Qi ◽

Dirk Feldmeyer

Keyword(s):

Barrel Cortex ◽

Dynamic Properties ◽

Pyramidal Cells ◽

Synaptic Connections ◽

Cell Type ◽

Short Term ◽

Electrophysiological Properties ◽

Cell Type Specific ◽

Feedback Networks ◽

Whole Cell Recordings

Neocortical layer 6 plays a crucial role in sensorimotor coordination and integration through functionally segregated circuits linking intracortical and subcortical areas. However, because of the high neuronal heterogeneity and sparse intralaminar connectivity data on the cell-type specific synaptic microcircuits in layer 6 remain few and far between. To address this issue, whole-cell recordings combined with morphological reconstructions have been used to identify morphoelectric types of layer 6A pyramidal cells (PCs) in rat barrel cortex. Cortico-thalamic (CT), corticocortical (CC) and cortico-claustral (CCla) pyramidal cells have been distinguished based on to their distinct dendritic and axonal morphologies as well as their different electrophysiological properties. Here we demonstrate that these three types of layer 6A pyramidal cells innervate neighboring excitatory neurons with distinct synaptic properties: CT PCs establish weak facilitating synapses to other L6A PCs; CC PCs form synapses of moderate efficacy; while synapses made by putative CCla PCs display the highest release probability and a marked short-term depression. Furthermore, for excitatory-inhibitory synaptic connections in layer 6 we were able to show that both the presynaptic PC type and the postsynaptic interneuron type govern the dynamic properties of the of the respective synaptic connections. We have identified a functional division of local layer 6A excitatory microcircuits which may be responsible of the differential temporal engagement of layer 6 feed-forward and feedback networks. Our results provides a basis for further investigations on the long-range cortico-cortical, cortico-thalamic and cortico-claustral pathways.

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Synchronized gamma-frequency inhibition in neocortex depends on excitatory-inhibitory interactions but not electrical synapses

Journal of Neurophysiology ◽

10.1152/jn.00071.2016 ◽

2016 ◽

Vol 116 (2) ◽

pp. 351-368 ◽

Cited By ~ 9

Author(s):

Garrett T. Neske ◽

Barry W. Connors

Keyword(s):

Pyramidal Neurons ◽

Barrel Cortex ◽

Pyramidal Cells ◽

Inhibitory Interneurons ◽

Electrical Synapses ◽

Postsynaptic Currents ◽

Gamma Frequency ◽

Up States ◽

Inhibitory Interactions

Synaptic inhibition plays a crucial role in the precise timing of spiking activity in the cerebral cortex. Synchronized, rhythmic inhibitory activity in the gamma (30–80 Hz) range is thought to be especially important for the active, information-processing neocortex, but the circuit mechanisms that give rise to synchronized inhibition are uncertain. In particular, the relative contributions of reciprocal inhibitory connections, excitatory-inhibitory interactions, and electrical synapses to precise spike synchrony among inhibitory interneurons are not well understood. Here we describe experiments on mouse barrel cortex in vitro as it spontaneously generates slow (<1 Hz) oscillations (Up and Down states). During Up states, inhibitory postsynaptic currents (IPSCs) are generated at gamma frequencies and are more synchronized than excitatory postsynaptic currents (EPSCs) among neighboring pyramidal cells. Furthermore, spikes in homotypic pairs of interneurons are more synchronized than in pairs of pyramidal cells. Comparing connexin36 knockout and wild-type animals, we found that electrical synapses make a minimal contribution to synchronized inhibition during Up states. Estimations of the delays between EPSCs and IPSCs in single pyramidal cells showed that excitation often preceded inhibition by a few milliseconds. Finally, tonic optogenetic activation of different interneuron subtypes in the absence of excitation led to only weak synchrony of IPSCs in pairs of pyramidal neurons. Our results suggest that phasic excitatory inputs are indispensable for synchronized spiking in inhibitory interneurons during Up states and that electrical synapses play a minimal role.

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Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABAA Receptors with a Special Reference to Propofol/Barbiturate

International Journal of Molecular Sciences ◽

10.3390/ijms21020563 ◽

2020 ◽

Vol 21 (2) ◽

pp. 563

Author(s):

Youngnam Kang ◽

Mitsuru Saito ◽

Hiroki Toyoda

Keyword(s):

Sensory Neurons ◽

Alcohol Withdrawal ◽

Gabaa Receptors ◽

Withdrawal Syndrome ◽

Barrel Cortex ◽

Pyramidal Cells ◽

Alcohol Withdrawal Syndrome ◽

Regulatory Mechanisms ◽

Postsynaptic Currents ◽

Calcineurin Activity

It is known that desensitization of GABAA receptor (GABAAR)-mediated currents is paradoxically correlated with the slowdown of their deactivation, i.e., resensitization. It has been shown that an upregulation of calcineurin enhances the desensitization of GABAAR-mediated currents but paradoxically prolongs the decay phase of inhibitory postsynaptic currents/potentials without appreciable diminution of their amplitudes. The paradoxical correlation between desensitization and resensitization of GABAAR-mediated currents can be more clearly seen in response to a prolonged application of GABA to allow more desensitization, instead of brief pulse used in previous studies. Indeed, hump-like GABAAR currents were produced after a strong desensitization at the offset of a prolonged puff application of GABA in pyramidal cells of the barrel cortex, in which calcineurin activity was enhanced by deleting phospholipase C-related catalytically inactive proteins to enhance the desensitization/resensitization of GABAAR-mediated currents. Hump-like GABAAR currents were also evoked at the offset of propofol or barbiturate applications in hippocampal or sensory neurons, but not GABA applications. Propofol and barbiturate are useful to treat benzodiazepine/alcohol withdrawal syndrome, suggesting that regulatory mechanisms of desensitization/resensitization of GABAAR-mediated currents are important in understanding benzodiazepine/alcohol withdrawal syndrome. In this review, we will discuss the molecular and regulatory mechanisms underlying the desensitization and resensitization of GABAAR-mediated currents and their functional significances.

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