scholarly journals Distinct organization of two cortico-cortical feedback pathways

2020 ◽  
Author(s):  
Shan Shen ◽  
Xiaolong Jiang ◽  
Federico Scala ◽  
Jiakun Fu ◽  
Paul Fahey ◽  
...  

AbstractNeocortical feedback is critical for processes like attention, prediction, and learning. A mechanistic understanding of its function requires deciphering its cell-type wiring logic. Recent studies revealed a disinhibitory circuit between motor and sensory areas in mice, where feedback preferentially targets vasointestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif is a general cortico-cortical feedback organizing principle. Combining multiple simultaneous whole-cell recordings with optogenetics we found that in contrast to this wiring rule, feedback between the hierarchically organized visual areas (lateral-medial to V1) preferentially activated somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpened feed-forward excitation by eliciting a transient increase followed by a prolonged decrease in pyramidal firing rate under sustained feed-forward input. However, under feed-forward transient input, the motor-sensory feedback facilitated pyramidal cell bursting while visual feedback increased spike time precision. Our findings argue for multiple feedback motifs implementing different dynamic non-linear operations.

2021 ◽  
Author(s):  
Danqing Yang ◽  
Guanxiao Qi ◽  
Dirk Feldmeyer

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.


2020 ◽  
Author(s):  
Caitlin A. Murphy ◽  
Matthew I. Banks

ABSTRACTBackgroundWhile their behavioral effects are well-characterized, the mechanisms by which anaesthetics induce loss of consciousness are largely unknown. Anaesthetics may disrupt integration and propagation of information in corticothalamic networks. Recent studies have shown that isoflurane diminishes synaptic responses of thalamocortical (TC) and corticocortical (CC) afferents in a pathway-specific manner. However, whether the synaptic effects of isoflurane observed in extracellular recordings persist at the cellular level has yet to be explored.MethodsHere, we activate TC and CC layer 1 inputs in non-primary mouse neocortex in ex vivo brain slices and explore the degree to which isoflurane modulates synaptic responses in pyramidal cells and in two inhibitory cell populations, somatostatin-positive (SOM+) and parvalbumin-positive (PV+) interneurons.ResultsWe show that the effects of isoflurane on synaptic responses and intrinsic properties of these cells varies among cell type and by cortical layer. Layer 1 inputs to L4 pyramidal cells were suppressed by isoflurane at both TC and CC synapses, while those to L2/3 pyramidal cells and PV+ interneurons were not. TC inputs to SOM+ cells were rarely observed at all, while CC inputs to SOM+ interneurons were robustly suppressed by isoflurane.ConclusionsThese results suggest a mechanism by which isoflurane disrupts integration and propagation of thalamocortical and intracortical signals.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ali Karimi ◽  
Jan Odenthal ◽  
Florian Drawitsch ◽  
Kevin M Boergens ◽  
Moritz Helmstaedter

We investigated the synaptic innervation of apical dendrites of cortical pyramidal cells in a region between layers (L) 1 and 2 using 3-D electron microscopy applied to four cortical regions in mouse. We found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 2-fold larger for L2 than L3 and L5 thick-tufted pyramidal cells. Towards the distal tuft dendrites in upper L1, the relative inhibitory input was at least about 2-fold larger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input fraction. The inhibitory-to-excitatory synaptic ratio is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either L2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites and support differential computational properties of L2, L3 and subtypes of L5 pyramidal cells in cortex.


1998 ◽  
Vol 80 (6) ◽  
pp. 2836-2847 ◽  
Author(s):  
F. Morin ◽  
C. Beaulieu ◽  
J.-C. Lacaille

Morin, F., C. Beaulieu, and J.-C. Lacaille. Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. J. Neurophysiol. 80: 2836–2847, 1998. Hippocampal sclerosis and hyperexcitability are neuropathological features of human temporal lobe epilepsy that are reproduced in the kainic acid (KA) model of epilepsy in rats. To assess directly the role of inhibitory interneurons in the KA model, the membrane and synaptic properties of interneurons located in 1) stratum oriens near the alveus (O/A) and 2) at the border of stratum radiatum and stratum lacunosum-moleculare (LM), as well as those of pyramidal cells, were examined with whole cell recordings in slices of control and KA-lesioned rats. In current-clamp recordings, intrinsic cell properties such as action potential amplitude and duration, amplitude of fast and medium duration afterhyperpolarizations, membrane time constant, and input resistance were generally unchanged in all cell types after KA treatment. In voltage-clamp recordings, the amplitude and conductance of pharmacologically isolated excitatory postsynaptic currents (EPSCs) were significantly reduced in LM interneurons of KA-treated animals but were not significantly changed in O/A and pyramidal cells. The rise time of EPSCs was not significantly changed in any cell type after KA treatment. In contrast, the decay time constant of EPSCs was significantly faster in O/A interneurons of KA-treated rats but was unchanged in LM and pyramidal cells. The amplitude and conductance of pharmacologically isolated γ-aminobutyric acid-A (GABAA) inhibitory postsynaptic currents (IPSCs) were not significantly changed in any cell type of KA-treated rats. The rise time and decay time constant of GABAA IPSCs were significantly faster in pyramidal cells of KA-treated rats but were not significantly changed in O/A and LM interneurons. These results suggest that complex alterations in synaptic currents occur in specific subpopulations of inhibitory interneurons in the CA1 region after KA lesions. A reduction of evoked excitatory drive onto inhibitory cells located at the border of stratum radiatum and stratum lacunosum-moleculare may contribute to disinhibition and polysynaptic epileptiform activity in the CA1 region. Compensatory changes, involving excitatory synaptic transmission on other interneuron subtypes and inhibitory synaptic transmission on pyramidal cells, may also take place and contribute to the residual, functional monosynaptic inhibition observed in principal cells after KA treatment.


2013 ◽  
Vol 110 (8) ◽  
pp. 1930-1944 ◽  
Author(s):  
Franck Dubruc ◽  
David Dupret ◽  
Olivier Caillard

In the hippocampus, activity-dependent changes of synaptic transmission and spike-timing coordination are thought to mediate information processing for the purpose of memory formation. Here, we investigated the self-tuning of intrinsic excitability and spiking reliability by CA1 hippocampal pyramidal cells via changes of their GABAergic inhibitory inputs and endocannabinoid (eCB) signaling. Firing patterns of CA1 place cells, when replayed in vitro, induced an eCB-dependent transient reduction of spontaneous GABAergic activity, sharing the main features of depolarization-induced suppression of inhibition (DSI), and conditioned a transient improvement of spike-time precision during consecutive burst discharges. When evaluating the consequences of DSI on excitatory postsynaptic potential (EPSP)-spike coupling, we found that transient reductions of uncorrelated (spontaneous) or correlated (feedforward) inhibition improved EPSP-spike coupling probability. The relationship between EPSP-spike-timing reliability and inhibition was, however, more complex: transient reduction of correlated (feedforward) inhibition disrupted or improved spike-timing reliability according to the initial spike-coupling probability. Thus eCB-mediated tuning of pyramidal cell spike-time precision is governed not only by the initial level of global inhibition, but also by the ratio between spontaneous and feedforward GABAergic activities. These results reveal that eCB-mediated self-tuning of spike timing by the discharge of pyramidal cells can constitute an important contribution to place-cell assemblies and memory formation in the hippocampus.


2003 ◽  
Vol 90 (5) ◽  
pp. 2964-2972 ◽  
Author(s):  
Roman Tyzio ◽  
Anton Ivanov ◽  
Cristophe Bernard ◽  
Gregory L. Holmes ◽  
Yehezkiel Ben-Ari ◽  
...  

A depolarized resting membrane potential has long been considered to be a universal feature of immature neurons. Despite the physiological importance, the underlying mechanisms of this developmental phenomenon are poorly understood. Using perforated-patch, whole cell, and cell-attached recordings, we measured the membrane potential in CA3 pyramidal cells in hippocampal slices from postnatal rats. With gramicidin perforated-patch recordings, membrane potential was –44 ± 4 (SE) mV at postnatal days P0–P2, and it progressively shifted to –67 ± 2 mV at P13–15. A similar developmental change of the membrane potential has been also observed with conventional whole cell recordings. However, the value of the membrane potential deduced from the reversal potential of N-methyl-d-aspartate channels in cell-attached recordings did not change with age and was –77 ± 2 mV at P2 and –77 ± 2 mV at P13–14. The membrane potential measured using whole cell recordings correlated with seal and input resistance, being most depolarized in neurons with high, several gigaohms, input resistance and low seal resistance. Simulations revealed that depolarized values of the membrane potential in whole cell and perforated-patch recordings could be explained by a shunt through the seal contact between the pipette and membrane. Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development.


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