Increased Synaptic Strength and mGlu 2/3 Receptor Plasticity on Mouse Prefrontal Cortex Intratelencephalic Pyramidal Cells Following Intermittent Access to Ethanol

AbstractPeripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.

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

Cerebral Cortex ◽

10.1093/cercor/bhaa074 ◽

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.

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Dopaminergic Modulation of Local Network Activity in Rat Prefrontal Cortex

Journal of Neurophysiology ◽

10.1152/jn.00898.2006 ◽

2007 ◽

Vol 97 (6) ◽

pp. 4120-4128 ◽

Cited By ~ 31

Author(s):

Susanta Bandyopadhyay ◽

John J. Hablitz

Keyword(s):

Prefrontal Cortex ◽

Synaptic Transmission ◽

Receptor Agonist ◽

Neuronal Networks ◽

Brain Slices ◽

Pyramidal Cells ◽

Network Activity ◽

Lateral Spread ◽

Local Network ◽

Evoked Activity

Dopamine modulates prefrontal cortex excitability in complex ways. Dopamine's net effect on local neuronal networks is therefore difficult to predict based on studies on pharmacologically isolated excitatory or inhibitory connections. In the present work, we have studied the effects of dopamine on evoked activity in acute rat brain slices when both excitation and inhibition are intact. Whole cell recordings from layer II/III pyramidal cells under conditions of normal synaptic transmission showed that bath-applied dopamine (30 μM) increased the outward inhibitory component of composite postsynaptic currents, whereas inward excitatory currents were not significantly affected. Optical imaging with the voltage-sensitive dye N-(3-(triethylammonium)propyl)-4-(4-(p-diethylaminophenyl)buta-dienyl)pyridinium dibromide revealed that bath application of dopamine significantly decreased the amplitude, duration, and lateral spread of activity in local cortical networks. This effect of dopamine was observed both with single and train (5 at 20 Hz) stimuli. The effect was mimicked by the D1-like receptor agonist R(+)-6-chloro-7,8-dihydroxy-1-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1 μM) and was blocked by R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (10 μM), a selective antagonist for D1-like receptors. The D2-like receptor agonist quinpirole (10 μM) had no significant effect on evoked dye signals. Our results suggest that dopamine's effect on inhibition dominates over that on excitation under conditions of normal synaptic transmission. Such neuromodulation by dopamine may be important for maintenance of stability in local neuronal networks in the prefrontal cortex.

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Electrophysiological Diversity of Layer 5 Pyramidal Cells in the Prefrontal Cortex of the Rhesus Monkey: In Vitro Slice Studies

Journal of Neurophysiology ◽

10.1152/jn.00585.2007 ◽

2007 ◽

Vol 98 (5) ◽

pp. 2622-2632 ◽

Cited By ~ 34

Author(s):

Yu-Ming Chang ◽

Jennifer I. Luebke

Keyword(s):

Prefrontal Cortex ◽

Rhesus Monkey ◽

Spike Train ◽

Pyramidal Cells ◽

Cell Types ◽

Dendritic Morphology ◽

Firing Patterns ◽

Electrophysiological Properties ◽

Whole Cell Patch Clamp

Whole cell patch-clamp recordings were employed to characterize the electrophysiological properties of layer 5 pyramidal cells in slices of the prefrontal cortex (Area 46) of the rhesus monkey. Four electrophysiologically distinct cell types were discriminated based on distinctive repetitive action potential (AP) firing patterns and single AP characteristics: regular-spiking slowly adapting type-1 cells (RS1; 62%), regular-spiking slowly adapting type-2 cells (RS2; 18%), regular-spiking fast-adapting cells (FA; 15%), and intrinsically bursting cells (IB; 5%). These cells did not differ with regard to their location in layer 5 nor in their dendritic morphology. In RS1 cells, AP threshold and amplitude did not change significantly during a 2-s spike train, whereas in RS2 and FA cells, AP threshold increased significantly and AP amplitude decreased significantly during the train. In FA cells, complete adaptation of AP firing was observed within 600 ms. IB cells displayed an all-or-none burst of three to six APs, followed by RS1-type firing behavior. RS1 cells could be further subdivided into three subtypes. Low-threshold spiking (LTS) RS1 cells exhibited an initial doublet riding on a depolarizing potential at the onset of a spike train and a prominent depolarizing afterpotential (DAP); intermediate RS1 cells (IM) exhibited a DAP, but no initial doublet, and non-LTS RS1 cells exhibited neither a DAP nor an initial doublet. RS2 and FA cells did not exhibit a DAP or initial doublets. The distinctive firing patterns of these diverse layer 5 pyramidal cells may reflect different roles played by these cells in the mediation of subcortical neuronal activity by the dorsolateral PFC.

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