Input To Pyramidal Neurons Research Articles

Selective activation of BK channels in small-headed dendritic spines suppresses excitatory postsynaptic potentials.

Dendritic spines are the main receptacles of excitatory information in the brain. Their particular morphology, with a small head connected to the dendrite by a slender neck, has inspired theoretical and experimental work to understand how these structural features affect the processing, storage and integration of synaptic inputs in pyramidal neurons (PNs). The activation of glutamate receptors in spines triggers a large voltage change as well as calcium signals at the spine head. Thus, voltage-gated and calcium-activated potassium channels located in the spine head likely play a key role in synaptic transmission. Here we study the presence and function of large conductance calcium-activated potassium (BK) channels in spines from layer 5 PNs. We found that BK channels are localized to dendrites and spines regardless of their size, but their activity can only be detected in spines with small head volumes (≤0.09μm3 ), which reduces the amplitude of two-photon uncaging excitatory postsynaptic potentials recorded at the soma. In addition, we found that calcium signals in spines with small head volumes are significantly larger than those observed in spines with larger head volumes. In accordance with our experimental data, numerical simulations predict that synaptic inputs impinging onto spines with small head volumes generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, which are sufficient to activate spine BK channels. These results show that BK channels are selectively activated in small-headed spines, suggesting a new level of dendritic spine-mediated regulation of synaptic processing, integration and plasticity in cortical PNs. KEY POINTS: BK channels are expressed in the visual cortex and layer 5 pyramidal neuron somata, dendrites and spines regardless of their size. BK channels are selectively activated in small-headed spines (≤0.09μm3 ), which reduces the amplitude of two-photon (2P) uncaging excitatory postsynaptic potentials (EPSPs) recorded at the soma. Two-photon imaging revealed that intracellular calcium responses in the head of 2P-activated spines are significantly larger in small-headed spines (≤0.09μm3 ) than in spines with larger head volumes. In accordance with our experimental data, numerical simulations showed that synaptic inputs impinging onto spines with small head volumes (≤0.09μm3 ) generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with larger head volumes, sufficient to activate spine BK channels and suppress EPSPs.

Multimodal description of whole brain connectivity: A comparison of resting state MEG, fMRI, and DWI.

Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion‐weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood‐oxygenation level‐dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI‐FC, and MEG‐FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI‐FC, and MEG‐FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI‐FC; SC and MEG‐FC at theta, alpha, beta and gamma bands; and fMRI‐FC and MEG‐FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance. Hum Brain Mapp 37:20–34, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Input transformation by dendritic spines of pyramidal neurons.

In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike.

An arithmetic rule for spatial summation of excitatory and inhibitory inputs in pyramidal neurons

Dendritic integration of excitatory and inhibitory inputs is critical for neuronal computation, but the underlying rules remain to be elucidated. Based on realistic modeling and experiments in rat hippocampal slices, we derived a simple arithmetic rule for spatial summation of concurrent excitatory glutamatergic inputs (E) and inhibitory GABAergic inputs (I). The somatic response can be well approximated as the sum of the excitatory postsynaptic potential (EPSP), the inhibitory postsynaptic potential (IPSP), and a nonlinear term proportional to their product (k*EPSP*IPSP), where the coefficient k reflects the strength of shunting effect. The k value shows a pronounced asymmetry in its dependence on E and I locations. For I on the dendritic trunk, k decays rapidly with E-I distance for proximal Es, but remains largely constant for distal Es, indicating a uniformly high shunting efficacy for all distal Es. For I on an oblique branch, the shunting effect is restricted mainly within the branch, with the same proximal/distal asymmetry. This asymmetry can be largely attributed to cable properties of the dendrite. Further modeling studies showed that this rule also applies to the integration of multiple coincident Es and Is. Thus, this arithmetic rule offers a simple analytical tool for studying E-I integration in pyramidal neurons that incorporates the location specificity of GABAergic shunting inhibition.

What are the mechanisms underlying the involvement of different subtypes of NMDA receptors in inducing long-term potentiation and depression in the hippocampus?

It has been hypothesized that the sign (direction) of modification of the efficiency of synaptic transmission depends on the subtype of N-methyl-D-aspartate (NMDA)-sensitive receptors involved. Activation of NMDA receptors with 2A subunits facilitates the induction of long-term potentiation, while receptors with 2B subunits facilitate the induction of long-term depression. However, experimental data have been obtained which contradict this hypothesis. We suggest an alternative hypothesis to explain currently available data. According to this hypothesis, activation of NMDA receptors containing different subunits can lead both to long-term potentiation and long-term depression, depending on the post-tetanic increase in the postsynaptic Ca(2+) concentration relative to the increase induced by preceding stimulation. Activation of NMDA receptors containing 2B subunits can lead to long-term depression of the excitatory input to pyramidal neurons because of the presence of these receptors on inhibitory interneurons, with induction of long-term potentiation on the interneuron and potentiation of inhibitory transmission between interneurons and pyramidal cells.