Postsynaptic Mechanisms Govern the Differential Excitation of Cortical Neurons by Thalamic Inputs

Hull, Court; Isaacson, Jeffry S.; Scanziani, Massimo

doi:10.1523/jneurosci.5971-08.2009

Cited by 129 publications

(160 citation statements)

References 56 publications

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“…The amplitude, per se, of ChR2-EPSCs showed considerable variability across experiments, presumably reflecting variability in the number of transduced axons contacting the recorded neurons, and was therefore a poor metric to quantify unitary synapse strengths. We thus substituted extracellular Ca 2+ for strontium (Sr 2+ ) because this manipulation results in asynchronous, input-specific, unitary AMPAR-mediated EPSCs (16,17). In these conditions, LED stimulation led to a time-locked, early ChR2-EPSC that was closely followed by several delayed, asynchronous EPSCs (asEPSCs) whose frequency was above the frequency of spontaneous EPSCs for ∼300 ms following LED stimulation ( Fig.…”

Section: +mentioning

confidence: 99%

Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

Geddes

Assadzada

Lemelin

et al. 2016

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

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Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation. Here, we found that the mPFC provides a direct monosynaptic, glutamatergic drive to both DRN 5-HT and GABA neurons and that this architecture was conducive to a robust feed-forward inhibition. Remarkably, activation of cannabinoid (CB) receptors differentially modulated the mPFC inputs onto these cell types in the DRN, in effect regulating the synaptic excitatory/inhibitory balance governing the excitability of 5-HT neurons. Thus, the CB system dynamically reconfigures the processing features of the DRN, a mood-related circuit believed to provide a concerted and distributed regulation of the excitability of large ensembles of brain networks.optogenetics | synapse | glutamate receptors | anxiety | depression T he phylogenetically old neurotransmitter serotonin (5-HT) is known to regulate a remarkably wide range of brain functions and behaviors, such as mood, aggression, reward, perception, levels of arousal, and decision making (1-5). The 5-HT-containing neurons are localized in a collection of small brainstem nuclei collectively known as the raphe nuclei, with the largest being the dorsal raphe nucleus (DRN). These neurons send extensive and widespread axonal projections throughout the forebrain (6). As such, the firing of a relatively small number of 5-HT neurons is powerfully poised to regulate the excitability of large ensembles of neural networks distributed across virtually the entire brain. However, little is known about how the synaptic networks impinging onto the DRN regulate the excitability of its constituent cells to generate the core feature selectivity of 5-HT neurons and, ultimately, to regulate the dynamic output of 5-HT to the brain. A significant step forward in this direction has recently been achieved by a number of anatomical studies that provide a comprehensive list of the brain regions projecting to the DRN, as well as detailed cartography of the connectivity patterns of these inputs to local cellular elements within the DRN subnetwork (i.e., 5-HT neurons, local GABAergic neurons) (7-9). The top-down control exerted by the phylogenetically recent medial prefrontal cortex (mPFC) over the DRN is of particular importance, in part, because of the purported role of this pathway in regulating several aspects of motivation and stress processing, and in mediating antidepressant-like effects (1, 10, 11). The mechanistic details of this long-range connectivity are elusive, howe...

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Section: +mentioning

confidence: 99%

Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

Geddes

Assadzada

Lemelin

et al. 2016

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

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“…Interneurons express NMDARs, and synaptic NMDARmediated excitatory postsynaptic currents increase robustly between P6 and P8-10 (Zhang and Sun, 2011). Later, interneurons downregulate NMDAR currents (Wang and Gao, 2010), which could explain why NMDARs play no role in the recruitment of feed-forward inhibition by adult thalamocortical inputs (Hull et al, 2009;Ling and Benardo, 1995). A recent study shows that depleting the GluN1 subunit from postnatal corticolimbic interneurons causes a schizophrenia-like phenotype, with a loss of Gad67 and parvalbumin expression and deficits in inhibition (Belforte et al, 2010).…”

Section: Nmdars and Vgccs Mediate Dendritic Growth Triggered By Selecmentioning

confidence: 99%

Cell class-specific regulation of neocortical dendrite and spine growth by AMPA receptor splice and editing variants

et al. 2011

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SUMMARYGlutamatergic transmission converging on calcium signaling plays a key role in dendritic differentiation. In early development, AMPA receptor (AMPAR) transcripts are extensively spliced and edited to generate subunits that differ in their biophysical properties. Whether these subunits have specific roles in the context of structural differentiation is unclear. We have investigated the role of nine GluA variants and revealed a correlation between the expression of flip variants and the period of major dendritic growth. In interneurons, only GluA1(Q)-flip increased dendritic length and branching. In pyramidal cells, GluA2(Q)-flop, GluA2(Q)-flip, GluA3(Q)-flip and calcium-impermeable GluA2(R)-flip promoted dendritic growth, suggesting that flip variants with slower desensitization kinetics are more important than receptors with elevated calcium permeability. Imaging revealed significantly higher calcium signals in pyramidal cells transfected with GluA2(R)-flip as compared with GluA2(R)-flop, suggesting a contribution of voltage-activated calcium channels. Indeed, dendritic growth induced by GluA2(R)-flip in pyramidal cells was prevented by blocking NMDA receptors (NMDARs) or voltage-gated calcium channels (VGCCs), suggesting that they act downstream of AMPARs. Intriguingly, the action of GluA1(Q)-flip in interneurons was also dependent on NMDARs and VGCCs. Cell class-specific effects were not observed for spine formation, as GluA2(Q)-flip and GluA2(Q)-flop increased spine density in pyramidal cells as well as in interneurons. The results suggest that AMPAR variants expressed early in development are important determinants for activity-dependent dendritic growth in a cell type-specific and cell compartment-specific manner.

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“…Thalamocortical synapses onto fast-spike interneurons are even more powerful than those onto spiny cells of layer 4 (Gibson and Connors, 1999;Cruikshank et al, 2007;Hull et al, 2009). Here, we showed that even those SINs receiving powerful input from an LGNd neuron (Fig.…”

Section: Previous Studies Of Cortical Neurons Across Awake Substatesmentioning

confidence: 99%

Getting Drowsy? Alert/Nonalert Transitions and Visual Thalamocortical Network Dynamics

Bereshpolova¹,

Stoelzel²,

Zhuang³

et al. 2011

J. Neurosci.

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The effects of different EEG brain states on spontaneous firing of cortical populations are not well understood. Such state shifts may occur frequently under natural conditions, and baseline firing patterns can impact neural coding (e.g., signal-to-noise ratios, sparseness of coding). Here, we examine the effects of spontaneous transitions from alert to nonalert awake EEG states in the rabbit visual cortex (5 s before and after the state-shifts). In layer 4, we examined putative spiny neurons and fast-spike GABAergic interneurons; in layer 5, we examined corticotectal neurons. We also examined the behavior of retinotopically aligned dorsal lateral geniculate nucleus (LGNd) neurons, usually recorded simultaneously with the above cortical populations. Despite markedly reduced firing and sharply increased bursting in the LGNd neurons following the transition to the nonalert state, little change occurred in the spiny neurons of layer 4. However, fast-spike neurons of layer 4 showed a paradoxical increase in firing rates as thalamic drive decreased in the nonalert state, even though some of these cells received potent monosynaptic input from the same LGNd neurons whose rates were reduced. The firing rates of corticotectal neurons of layer 5, similarly to spiny cells of layer 4, were not state-dependent, but these cells did become more bursty in the nonalert state, as did the fast-spike cells. These results show that spontaneous firing rates of midlayer spiny populations are remarkably conserved following the shift from alert to nonalert states, despite marked reductions in excitatory thalamic drive and increased activity in local fast-spike inhibitory interneurons.

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Postsynaptic Mechanisms Govern the Differential Excitation of Cortical Neurons by Thalamic Inputs

Cited by 129 publications

References 56 publications

Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

Cell class-specific regulation of neocortical dendrite and spine growth by AMPA receptor splice and editing variants

Getting Drowsy? Alert/Nonalert Transitions and Visual Thalamocortical Network Dynamics

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