Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex

Neuroscience ◽  
2004 ◽  
Vol 125 (1) ◽  
pp. 277-288 ◽  
Author(s):  
J.I Luebke ◽  
Y.-M Chang ◽  
T.L Moore ◽  
D.L Rosene
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Cells ◽  
Normal Aging ◽  
Synaptic Inhibition ◽  
Synaptic Excitation ◽  
Layer 2 ◽  
Monkey Prefrontal Cortex

scholarly journals Electrophysiological classes of layer 2/3 pyramidal cells in monkey prefrontal cortex

2012 ◽  
Vol 108 (2) ◽  
pp. 595-609 ◽  
Author(s):  
A. V. Zaitsev ◽  
N. V. Povysheva ◽  
G. Gonzalez-Burgos ◽  
D. A. Lewis
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Functional Properties ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Spiking Neurons ◽  
Membrane Properties ◽  
Layer 2 ◽  
Monkey Prefrontal Cortex ◽  
Intrinsic Membrane Properties

The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. Therefore, the intrinsic membrane properties, a crucial determinant of a neuron's functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.

scholarly journals Developmental Regulation of Basket Interneuron Synapses and Behavior through NCAM in Mouse Prefrontal Cortex

2020 ◽  
Vol 30 (8) ◽  
pp. 4689-4707
Author(s):  
Chelsea S Sullivan ◽  
Vishwa Mohan ◽  
Paul B Manis ◽  
Sheryl S Moy ◽  
Young Truong ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Developmental Regulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Electrophysiological Recording ◽  
Network Function ◽  
Growth Cone Collapse ◽  
Layer 2 ◽  
And Behavior

Abstract Parvalbumin (PV)-expressing basket interneurons in the prefrontal cortex (PFC) regulate pyramidal cell firing, synchrony, and network oscillations. Yet, it is unclear how their perisomatic inputs to pyramidal neurons are integrated into neural circuitry and adjusted postnatally. Neural cell adhesion molecule NCAM is expressed in a variety of cells in the PFC and cooperates with EphrinA/EphAs to regulate inhibitory synapse density. Here, analysis of a novel parvalbumin (PV)-Cre: NCAM F/F mouse mutant revealed that NCAM functions presynaptically in PV+ basket interneurons to regulate postnatal elimination of perisomatic synapses. Mutant mice exhibited an increased density of PV+ perisomatic puncta in PFC layer 2/3, while live imaging in mutant brain slices revealed fewer puncta that were dynamically eliminated. Furthermore, EphrinA5-induced growth cone collapse in PV+ interneurons in culture depended on NCAM expression. Electrophysiological recording from layer 2/3 pyramidal cells in mutant PFC slices showed a slower rise time of inhibitory synaptic currents. PV-Cre: NCAM F/F mice exhibited impairments in working memory and social behavior that may be impacted by altered PFC circuitry. These findings suggest that the density of perisomatic synapses of PV+ basket interneurons is regulated postnatally by NCAM, likely through EphrinA-dependent elimination, which is important for appropriate PFC network function and behavior.

Cluster Analysis–Based Physiological Classification and Morphological Properties of Inhibitory Neurons in Layers 2–3 of Monkey Dorsolateral Prefrontal Cortex

2005 ◽  
Vol 94 (5) ◽  
pp. 3009-3022 ◽  
Author(s):  
Leonid S. Krimer ◽  
Aleksey V. Zaitsev ◽  
Gabriela Czanner ◽  
Sven Kröner ◽  
Guillermo González-Burgos ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Pyramidal Cells ◽  
Inhibitory Neurons ◽  
Morphological Properties ◽  
Electrophysiological Properties ◽  
Dorsolateral Prefrontal ◽  
Fast Spiking ◽  
Monkey Prefrontal Cortex

In primates, little is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 2–3 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.

scholarly journals mGluR1, but not mGluR5, activates feed-forward inhibition in the medial prefrontal cortex to impair decision making

2011 ◽  
Vol 106 (2) ◽  
pp. 960-973 ◽  
Author(s):  
Hao Sun ◽  
Volker Neugebauer
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Metabotropic Glutamate Receptors ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Synaptic Inhibition ◽  
Feed Forward ◽  
Postsynaptic Currents ◽  
Group I ◽  
Feed Forward Inhibition

Cognitive flexibility depends on the integrity of the prefrontal cortex (PFC). We showed previously that impaired decision making in pain results from amygdala-driven inhibition of medial PFC neurons, but the underlying mechanisms remain to be determined. Using whole cell patch clamp in rat brain slices and a cognitive behavioral task, we tested the hypothesis that group I metabotropic glutamate receptors (mGluRs) activate feed-forward inhibition to decrease excitability and output function of PFC pyramidal cells, thus impairing decision making. Polysynaptic inhibitory postsynaptic currents (IPSCs) and monosynaptic excitatory postsynaptic currents (EPSCs) were evoked in layer V pyramidal cells by stimulating presumed amygdala afferents. An mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine, DHPG] increased synaptic inhibition more strongly than excitatory transmission. The facilitatory effects were blocked by an mGluR1 [( S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, LY367385], but not mGluR5, antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine. IPSCs were blocked by bicuculline and decreased by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX). Facilitation of synaptic inhibition by DHPG was glutamate driven because it was blocked by NBQX. DHPG increased frequency but not amplitude of spontaneous IPSCs; consistent with action potential-dependent synaptic inhibition, tetrodotoxin (TTX) prevented the facilitatory effects. DHPG decreased synaptically evoked spikes (E-S coupling) and depolarization-induced spiking [frequency-current ( f-I) relationship]. This effect was indirect, resulting from glutamate-driven synaptic inhibition, because it persisted when a G protein blocker was included in the pipette but was blocked by GABAA receptor antagonists and NBQX. In contrast, DHPG increased E-S coupling and f-I relationships in mPFC interneurons through a presynaptic action, further supporting the concept of feed-forward inhibition. DHPG also impaired the ability of the animals to switch strategies in a decision-making task; bicuculline restored normal decision making, whereas a GABAA receptor agonist (muscimol) mimicked the decision-making deficit. The results show that mGluR1 activates feed-forward inhibition of PFC pyramidal cells to impair cognitive functions.

Inhibition of the slow afterhyperpolarization restores the classical spike timing-dependent plasticity rule obeyed in layer 2/3 pyramidal cells of the prefrontal cortex

2012 ◽  
Vol 107 (1) ◽  
pp. 205-215 ◽  
Author(s):  
Aleksey V. Zaitsev ◽  
Roger Anwyl
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Spike Timing Dependent Plasticity ◽  
Dependent Plasticity ◽  
Layer 2 ◽  
Stdp Rule ◽  
Stimulation Of

The induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory postsynaptic currents was investigated in proximal synapses of layer 2/3 pyramidal cells of the rat medial prefrontal cortex. The spike timing-dependent plasticity (STDP) induction protocol of negative timing, with postsynaptic leading presynaptic stimulation of action potentials (APs), induced LTD as expected from the classical STDP rule. However, the positive STDP protocol of presynaptic leading postsynaptic stimulation of APs predominantly induced a presynaptically expressed LTD rather than the expected postsynaptically expressed LTP. Thus the induction of plasticity in layer 2/3 pyramidal cells does not obey the classical STDP rule for positive timing. This unusual STDP switched to a classical timing rule if the slow Ca2+-dependent, K+-mediated afterhyperpolarization (sAHP) was inhibited by the selective blocker N-trityl-3-pyridinemethanamine (UCL2077), by the β-adrenergic receptor agonist isoproterenol, or by the cholinergic agonist carbachol. Thus we demonstrate that neuromodulators can affect synaptic plasticity by inhibition of the sAHP. These findings shed light on a fundamental question in the field of memory research regarding how environmental and behavioral stimuli influence LTP, thereby contributing to the modulation of memory.

scholarly journals Differential Synaptic Dynamics and Circuit Connectivity of Hippocampal and Thalamic Inputs to the Prefrontal Cortex

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Sarah Canetta ◽  
Eric Teboul ◽  
Emma Holt ◽  
Scott S Bolkan ◽  
Nancy Padilla-Coreano ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Vasoactive Intestinal Peptide ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Mediodorsal Nucleus ◽  
Layer 2 ◽  
Communication Frequency ◽  
Synaptic Dynamics ◽  
Subcortical Regions

Abstract The medial prefrontal cortex (mPFC) integrates inputs from multiple subcortical regions including the mediodorsal nucleus of the thalamus (MD) and the ventral hippocampus (vHPC). How the mPFC differentially processes these inputs is not known. One possibility is that these two inputs target discreet populations of mPFC cells. Alternatively, individual prefrontal cells could receive convergent inputs but distinguish between both inputs based on synaptic differences, such as communication frequency. To address this, we utilized a dual wavelength optogenetic approach to stimulate MD and vHPC inputs onto single, genetically defined mPFC neuronal subtypes. Specifically, we compared the convergence and synaptic dynamics of both inputs onto mPFC pyramidal cells, and parvalbumin (PV)- and vasoactive intestinal peptide (VIP)-expressing interneurons. We found that all individual pyramidal neurons in layer 2/3 of the mPFC receive convergent input from both MD and vHPC. In contrast, PV neurons receive input biased from the MD, while VIP cells receive input biased from the vHPC. Independent of the target, MD inputs transferred information more reliably at higher frequencies (20 Hz) than vHPC inputs. Thus, MD and vHPC projections converge functionally onto mPFC pyramidal cells, but both inputs are distinguished by frequency-dependent synaptic dynamics and preferential engagement of discreet interneuron populations.

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