scholarly journals Mechanisms underlying serotonergic excitation of callosal projection neurons

2017 ◽  
Author(s):  
Emily K. Stephens ◽  
Arielle L. Baker ◽  
Allan T. Gulledge
Keyword(s):  
Intracellular Calcium ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Projection Neurons ◽  
Calcium Dependent ◽  
M Current ◽  
Cation Conductance ◽  
Cortical Pyramidal Neurons ◽  
Excitatory Responses ◽  
Callosal Projection

AbstractSerotonin (5-HT) selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A) receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current), or activation of nonspecific cation conductances that underly calcium-dependent afterdepolarizations (ADPs). However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s) involved. We tested potential mechanisms of serotonergic excitation in commissural/callosal projection neurons (COM neurons) in layer 5 of the mouse medial prefrontal cortex, a subpopulation of cortical pyramidal neurons that exhibit 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh) receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%), rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances contributing to 2A excitation. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50% (i.e., back to normal baseline values) when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a nonspecific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third ionic effector, as blockade of KV7 channels with XE991 (10 μM) reduced serotonergic excitation by ∼50% in control conditions, and by ∼30% with intracellular BAPTA present. These findings demonstrate a role for at least three distinct ionic effectors, including KV7 channels, a calcium-sensitive and calcium-permeable nonspecific cation conductance, and the calcium-dependent ADP conductance, in mediating serotonergic excitation of COM neurons.

scholarly journals Preferential cholinergic excitation of corticopontine neurons

2017 ◽  
Author(s):  
Arielle L. Baker ◽  
Ryan J. O’Toole ◽  
Allan T. Gulledge
Keyword(s):  
Pyramidal Neurons ◽  
Projection Neurons ◽  
Triggered Release ◽  
Calcium Dependent ◽  
M Current ◽  
Cation Conductance ◽  
Specific Selectivity ◽  
Ionic Mechanisms ◽  
Excitatory Responses ◽  
And Behavior

AbstractPyramidal neurons in layer 5 of the neocortex comprise two broad classes of projection neurons: corticofugal neurons, including corticopontine (CPn) neurons, and intratelencephalic neurons, including commissural/callosal (COM) neurons. These non-overlapping neuron subpopulations represent discrete cortical output channels contributing to perception, decision making, and behavior. CPn and COM neurons have distinct morphological and physiological characteristics, and divergent responses to modulatory transmitters such as serotonin and acetylcholine (ACh). To better understand how ACh regulates cortical output, in slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron subtypes, exogenous ACh generated qualitatively similar biphasic responses in which brief hyperpolarization was followed by longer-lasting enhancement of excitability. However, cholinergic inhibition was more pronounced in COM neurons, while excitatory responses were larger and longer lasting in CPn neurons. Similarly, optically triggered release of endogenous ACh from cholinergic terminals preferentially and persistently (for ~40 s) enhanced the excitability of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of CPn neurons involved at least three distinct ionic mechanisms: activation of a calcium-sensitive but calcium-permeable nonspecific cation conductance, suppression of Kv7 channels (the “M-current”), and activation of the calcium-dependent nonspecific cation conductance underlying afterdepolarizations. Our results demonstrate projection-specific selectivity in cholinergic signaling in the PFC, and suggest that transient release of ACh during behavior will preferentially promote corticofugal output.

scholarly journals Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Yi ◽  
Tavita Garrett ◽  
Karl Deisseroth ◽  
Heikki Haario ◽  
Emily Stone ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Synaptic Depression ◽  
Medial Septum ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Calcium Dependent ◽  
Light Pulses ◽  
Diagonal Band ◽  
Initial Release ◽  
Intrinsic Membrane Properties

AbstractParvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ($$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB ) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neuronal properties. $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1–2 ms) 470 nm light pulses. To investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB transmission, light pulses at 5–50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ($$\hbox {PV}_{\text{HC}}$$ PV HC ) neurons generated trains of $$\hbox {PV}_{\text{HC}}$$ PV HC -mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to $$\hbox {PV}_{\text{HC}}$$ PV HC synapses, $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the $$\hbox {PV}_{\text{HC}}$$ PV HC model, the $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.

scholarly journals Increased Callosal Connectivity in Reeler Mice Revealed by Brain-Wide Input Mapping of VIP Neurons in Barrel Cortex

2020 ◽  
Author(s):  
Georg Hafner ◽  
Julien Guy ◽  
Mirko Witte ◽  
Pavel Truschow ◽  
Alina Rüppel ◽  
...  
Keyword(s):  
Long Range ◽  
Cortical Neurons ◽  
Barrel Cortex ◽  
Projection Neurons ◽  
Subcortical Structures ◽  
Virus Tracing ◽  
Cortical Inputs ◽  
Callosal Projection ◽  
To Receive ◽  
The Brain

Abstract The neocortex is composed of layers. Whether layers constitute an essential framework for the formation of functional circuits is not well understood. We investigated the brain-wide input connectivity of vasoactive intestinal polypeptide (VIP) expressing neurons in the reeler mouse. This mutant is characterized by a migration deficit of cortical neurons so that no layers are formed. Still, neurons retain their properties and reeler mice show little cognitive impairment. We focused on VIP neurons because they are known to receive strong long-range inputs and have a typical laminar bias toward upper layers. In reeler, these neurons are more dispersed across the cortex. We mapped the brain-wide inputs of VIP neurons in barrel cortex of wild-type and reeler mice with rabies virus tracing. Innervation by subcortical inputs was not altered in reeler, in contrast to the cortical circuitry. Numbers of long-range ipsilateral cortical inputs were reduced in reeler, while contralateral inputs were strongly increased. Reeler mice had more callosal projection neurons. Hence, the corpus callosum was larger in reeler as shown by structural imaging. We argue that, in the absence of cortical layers, circuits with subcortical structures are maintained but cortical neurons establish a different network that largely preserves cognitive functions.

scholarly journals The Effects of Spike Frequency Adaptation and Negative Feedback on the Synchronization of Neural Oscillators

2001 ◽  
Vol 13 (6) ◽  
pp. 1285-1310 ◽  
Author(s):  
Bard Ermentrout ◽  
Matthew Pascal ◽  
Boris Gutkin
Keyword(s):  
Cortical Neurons ◽  
Potassium Current ◽  
Spike Frequency ◽  
Repetitive Firing ◽  
Spike Frequency Adaptation ◽  
Calcium Dependent ◽  
M Current ◽  
Frequency Adaptation ◽  
Voltage Dependent ◽  
Standard Models

There are several different biophysical mechanisms for spike frequency adaptation observed in recordings from cortical neurons. The two most commonly used in modeling studies are a calcium-dependent potassium current Iahp and a slow voltage-dependent potassium current, Im. We show that both of these have strong effects on the synchronization properties of excitatorily coupled neurons. Furthermore, we show that the reasons for these effects are different. We show through an analysis of some standard models, that the M-current adaptation alters the mechanism for repetitive firing, while the after hyperpolarization adaptation works via shunting the incoming synapses. This latter mechanism applies with a network that has recurrent inhibition. The shunting behavior is captured in a simple two-variable reduced model that arises near certain types of bifurcations. A one-dimensional map is derived from the simplified model.

scholarly journals Single Cortical Neurons as Deep Artificial Neural Networks

2019 ◽  
Author(s):  
David Beniaguev ◽  
Idan Segev ◽  
Michael London
Keyword(s):  
Neural Networks ◽  
Cortical Neurons ◽  
Deep Neural Networks ◽  
Pyramidal Neurons ◽  
Classical Architecture ◽  
Novel Approach ◽  
Cortical Pyramidal Neurons ◽  
Spatio Temporal ◽  
Cortical Pyramidal Cell

AbstractWe introduce a novel approach to study neurons as sophisticated I/O information processing units by utilizing recent advances in the field of machine learning. We trained deep neural networks (DNNs) to mimic the I/O behavior of a detailed nonlinear model of a layer 5 cortical pyramidal cell, receiving rich spatio-temporal patterns of input synapse activations. A Temporally Convolutional DNN (TCN) with seven layers was required to accurately, and very efficiently, capture the I/O of this neuron at the millisecond resolution. This complexity primarily arises from local NMDA-based nonlinear dendritic conductances. The weight matrices of the DNN provide new insights into the I/O function of cortical pyramidal neurons, and the approach presented can provide a systematic characterization of the functional complexity of different neuron types. Our results demonstrate that cortical neurons can be conceptualized as multi-layered “deep” processing units, implying that the cortical networks they form have a non-classical architecture and are potentially more computationally powerful than previously assumed.

Suppression of Ih Contributes to Propofol-Induced Inhibition of Mouse Cortical Pyramidal Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 3872-3883 ◽  
Author(s):  
Xiangdong Chen ◽  
Shaofang Shu ◽  
Douglas A. Bayliss
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Current Amplitude ◽  
Hcn Channels ◽  
General Anesthetic ◽  
Large Shift ◽  
Fast Kinetics ◽  
Membrane Hyperpolarization ◽  
Cortical Pyramidal Neurons

The contributions of the hyperpolarization-activated current, Ih, to generation of rhythmic activities are well described for various central neurons, particularly in thalamocortical circuits. In the present study, we investigated effects of a general anesthetic, propofol, on native Ih in neurons of thalamus and cortex and on the corresponding cloned HCN channel subunits. Whole cell voltage-clamp recordings from mouse brain slices identified neuronal Ih currents with fast activation kinetics in neocortical pyramidal neurons and with slower kinetics in thalamocortical relay cells. Propofol inhibited the fast-activating Ih in cortical neurons at a clinically relevant concentration (5 μM); inhibition of Ih involved a hyperpolarizing shift in half-activation voltage (Δ V1/2 approximately −9 mV) and a decrease in maximal available current (∼36% inhibition, measured at −120 mV). With the slower form of Ih expressed in thalamocortical neurons, propofol had no effect on current activation or amplitude. In heterologous expression systems, 5 μM propofol caused a large shift in V1/2 and decrease in current amplitude in homomeric HCN1 and linked heteromeric HCN1–HCN2 channels, both of which activate with fast kinetics but did not affect V1/2 or current amplitude of slowly activating homomeric HCN2 channels. With GABAA and glycine receptor channels blocked, propofol caused membrane hyperpolarization and suppressed action potential discharge in cortical neurons; these effects were occluded by the Ih blocker, ZD-7288. In summary, these data indicate that propofol selectively inhibits HCN channels containing HCN1 subunits, such as those that mediate Ih in cortical pyramidal neurons—and they suggest that anesthetic actions of propofol may involve inhibition of cortical neurons and perhaps other HCN1-expressing cells.

scholarly journals Cell-type specific D1 dopamine receptor modulation of projection neurons and interneurons in the prefrontal cortex

2018 ◽  
Author(s):  
Paul G. Anastasiades ◽  
Christina Boada ◽  
Adam G. Carter
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
D1 Receptor ◽  
Receptor Expression ◽  
D1 Receptors ◽  
Projection Neurons ◽  
Specific Cell ◽  
Action Potential Firing ◽  
Receptor Modulation

ABSTRACTDopamine modulation in the prefrontal cortex (PFC) mediates diverse effects on neuronal physiology and function, but the expression of dopamine receptors at sub-populations of pyramidal neurons and interneurons remains unresolved. Here, we examine D1 receptor expression and modulation at specific cell types and layers in the mouse prelimbic PFC. We first show that D1 receptors are enriched in pyramidal neurons in both layers 5 and 6, and that these cells project intra-telencephalically, rather than to sub-cortical structures. We then find that D1 receptors are also present in interneurons, and enriched in VIP+ interneurons that co-expresses calretinin, but absent from PV+ and SOM+ interneurons. Finally, we determine that D1 receptors strongly and selectively enhance action potential firing in only a subset of these cortico-cortical neurons and VIP+ interneurons. Our findings define several novel sub-populations of D1+ neurons, highlighting how modulation via D1 receptors can influence both excitatory and disinhibitory micro-circuits in the PFC.

scholarly journals Distinct populations of cortical pyramidal neurons mediate drug reward and aversion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. F. Garcia ◽  
E. A. Crummy ◽  
I. G. Webb ◽  
M. N. Nooney ◽  
S. M. Ferguson
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Tract ◽  
Anterior Cingulate ◽  
Projection Neurons ◽  
Cortical Function ◽  
Drug Experience ◽  
Appropriate Behavior ◽  
Electrophysiological Properties ◽  
Chronic Drug Use ◽  
Cortical Pyramidal Neurons

AbstractProcessing within the anterior cingulate cortex (ACC) is crucial for the patterning of appropriate behavior, and ACC dysfunction following chronic drug use is thought to play a major role in drug addiction. However, cortical pyramidal projection neurons can be subdivided into two major types (intratelencephalic (IT) and pyramidal tract (PT)), with distinct inputs and projection targets, molecular and receptor profiles, morphologies and electrophysiological properties. Yet, how each of these cell populations modulate behavior related to addiction is unknown. We demonstrate that PT neurons regulate the positive features of a drug experience whereas IT neurons regulate the negative features. These findings support a revised theory of cortical function in addiction, with distinct cells and circuits mediating reward and aversion.

scholarly journals A functional spiking neuronal network for tactile sensing pathway to process edge orientation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adel Parvizi-Fard ◽  
Mahmood Amiri ◽  
Deepesh Kumar ◽  
Mark M. Iskarous ◽  
Nitish V. Thakor
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Receptive Fields ◽  
Population Level ◽  
Neural Model ◽  
Field Size ◽  
Projection Neurons ◽  
Cuneate Nucleus ◽  
Edge Orientation ◽  
Three Stages

AbstractTo obtain deeper insights into the tactile processing pathway from a population-level point of view, we have modeled three stages of the tactile pathway from the periphery to the cortex in response to indentation and scanned edge stimuli at different orientations. Three stages in the tactile pathway are, (1) the first-order neurons which innervate the cutaneous mechanoreceptors, (2) the cuneate nucleus in the midbrain and (3) the cortical neurons of the somatosensory area. In the proposed network, the first layer mimics the spiking patterns generated by the primary afferents. These afferents have complex skin receptive fields. In the second layer, the role of lateral inhibition on projection neurons in the cuneate nucleus is investigated. The third layer acts as a biomimetic decoder consisting of pyramidal and cortical interneurons that correspond to heterogeneous receptive fields with excitatory and inhibitory sub-regions on the skin. In this way, the activity of pyramidal neurons is tuned to the specific edge orientations. By modifying afferent receptive field size, it is observed that the larger receptive fields convey more information about edge orientation in the first spikes of cortical neurons when edge orientation stimuli move across the patch of skin. In addition, the proposed spiking neural model can detect edge orientation at any location on the simulated mechanoreceptor grid with high accuracy. The results of this research advance our knowledge about tactile information processing and can be employed in prosthetic and bio-robotic applications.

Changes in Membrane Potential and the Intracellular Calcium Concentration During CSD and OGD in Layer V and Layer II/III Mouse Cortical Neurons

2010 ◽  
Vol 104 (6) ◽  
pp. 3203-3212 ◽  
Author(s):  
Helen M. Gniel ◽  
Rosemary L. Martin
Keyword(s):  
Membrane Potential ◽  
Intracellular Calcium ◽  
Cortical Neurons ◽  
Calcium Concentration ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Glucose Deprivation ◽  
Intracellular Calcium Concentration ◽  
Neuronal Types ◽  
Layer V

Cortical spreading depression (CSD) is an episode of electrical silence following intense neuronal activity that propagates across the cortex at ∼3–6 mm/min and is associated with transient neuronal depolarization. CSD is benign in normally perfused brain tissue, but there is evidence suggesting that repetitive CSD contributes to infarct growth following focal ischemia. Studies to date have assumed that the cellular responses to CSD are uniform across neuronal types because there are no data to the contrary. In this study, we investigated the effect of CSD on membrane potential and the intracellular calcium concentration ([Ca2+]i) of mouse layer V and layer II/III pyramidal neurons in brain slices. To place the data in context, we made similar measurements during anoxic depolarization induced by oxygen and glucose deprivation (OGD). The [Ca2+]i was quantified using the low-affinity ratiometric indicator Fura-4F. During both CSD- and OGD-induced depolarization, the membrane potential approached 0 mV in all neurons. In layer V pyramids OGD resulted in an increase in [Ca2+]i to a maximum of 3.69 ± 0.73 (SD) μM ( n = 12), significantly greater than the increase to 1.81 ± 0.70 μM in CSD ( n = 34; P < 0.0001). Membrane potential and [Ca2+]i returned to nearly basal levels following CSD but not OGD. Layer II/III neurons responded to CSD with a greater peak increase in [Ca2+]i than layer V neurons (2.88 ± 0.6 μM; n = 9; P < 0.01). We conclude there is a laminar difference in the response of pyramidal neurons to CSD; possible explanations are discussed.

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