Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal cortex

Cannabinoids receptors have been reported to modulate synaptic transmission in many structures of the CNS, but yet little is known about their role in the prefrontal cortex where type I cannabinoid receptor (CB-1) are expressed. In this study, we tested first the acute effects of selective agonists and antagonist of CB-1 on glutamatergic excitatory postsynaptic currents (EPSCs) in slices of rat prefrontal cortex (PFC). EPSCs were evoked in patch-clamped layer V pyramidal cells by stimulation of layer V afferents. Monosynaptic EPSCs were strongly depressed by bath application (1 μM) of the cannabinoid receptors agonists WIN55212-2 (−50.4 ± 8.8%) and CP55940 (−42.4 ± 10.9%). The CB-1 antagonist SR141716A reversed these effects. Unexpectedly, SR141716A alone produced a significant increase of glutamatergic synaptic transmission (+46.9 ± 11.2%), which could be partly reversed by WIN55212-2. In the presence of strontium in the bath, the frequency but not the amplitude of asynchronous synaptic events evoked in layer V pyramidal cells by stimulating layer V afferents, was markedly decreased (−54.2 ± 8%), indicating a presynaptic site of action of cannabinoids at these synapses. Tetanic stimulation (100 pulses at 100 Hz, 4 trains) induced in control condition, no changes ( n = 7/18), long-term depression (LTD; n = 6/18), or long-term potentiation (LTP; n = 5/18) of monosynaptic EPSCs evoked by stimulation of layer V afferents. When tetanus was applied in the presence of WIN 55,212-2 or SR141716-A (1 μM) in the bath, the proportion of “nonplastic” cells were not significantly changed ( n = 7/15 in both cases). For the plastic ones ( n = 8 in both cases), WIN 55,212-2 strongly favored LTD ( n = 7/8) at the apparent expense of LTP ( n = 1/8), whereas the opposite effect was observed with SR141716-A (7/8 LTP; 1/8 LTD). These results demonstrate that cannabinoids influence glutamatergic synaptic transmission and plasticity in the PFC of rodent.

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Calcium-Activated Cation Nonselective Current Contributes to the Fast Afterdepolarization in Rat Prefrontal Cortex Neurons

Journal of Neurophysiology ◽

10.1152/jn.1997.78.4.1983 ◽

1997 ◽

Vol 78 (4) ◽

pp. 1983-1989 ◽

Cited By ~ 50

Author(s):

Samir Haj-Dahmane ◽

Rodrigo Andrade

Keyword(s):

Prefrontal Cortex ◽

Channel Blocker ◽

Reversal Potential ◽

Pyramidal Cells ◽

Channel Blockers ◽

Current Voltage ◽

Potassium Channel Blockers ◽

Layer V ◽

Firing Properties ◽

Hyperpolarizing Shift

Haj-Dahmane, Samir and Rodrigo Andrade. Calcium-activated cation nonselective current contributes to the fast afterdepolarization in rat prefrontal cortex neurons. J. Neurophysiol. 78: 1983–1989, 1997. Pyramidal cells of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) following an action potential. This ADP is blocked by replacing extracellular calcium with magnesium, by the application of the calcium-channel blocker cadmium, and by buffering intracellular calcium at near physiological levels. Thus this fast ADP appears mediated by a calcium-activated current. A prominent ADP is also observed following a calcium spike recorded in the presence of tetrodotoxin. The current underlying this ADP was recorded using a hybrid current-voltage protocol. A strong ADP could be observed in the presence of potassium channel blockers as well as at ECl. Furthermore, the current underlying the ADP increased with hyperpolarization in the subthreshold range and displayed an extrapolated reversal potential near +30 mV. Reducing the ratio of extracellular to intracellular sodium inhibited the current underlying the ADP and caused a hyperpolarizing shift in its reversal potential. We conclude that these cells express a calcium-activated cation nonselective current whose activation contributes to the generation of the fADP. This current could play an important role in determining the firing properties of pyramidal cells in cortex.

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Astrocyte expression of D2-like dopamine receptors in the prefrontal cortex

Translational Neuroscience ◽

10.2478/v10134-010-0035-6 ◽

2010 ◽

Vol 1 (3) ◽

Cited By ~ 7

Author(s):

Mihovil Mladinov ◽

Davor Mayer ◽

Luka Brčić ◽

Elizabeth Wolstencroft ◽

Nguyen Man ◽

...

Keyword(s):

Prefrontal Cortex ◽

Dopamine Receptors ◽

Glial Cells ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Tissue Samples ◽

Strong Expression ◽

Layer V ◽

The Right ◽

Protoplasmic Astrocytes

AbstractThe dopaminergic system is of crucial importance for understanding human behavior and the pathogenesis of many psychiatric and neurological conditions. The majority of studies addressing the localization of dopamine receptors (DR) examined the expression of DR in neurons, while its expression, precise anatomical localization and possible function in glial cells have been largely neglected. Here we examined the expression of D2-like family of DR in neuronal and glial cells in the normal human brain using immunocytochemistry and immunofluorescence. Tissue samples from the right orbitomedial (Brodmann’s areas 11/12), dorsolateral (areas 9/46) and dorsal medial (area 9) prefrontal cortex were taken during autopsy from six subjects with no history of neurological or psychiatric disorders, formalin-fixed, and embedded in paraffin. The sections were stained using novel anti-DRD2, anti-DRD3, and anti-DRD4 monoclonal antibodies. Adjacent sections were labeled with an anti-GFAP (astroglial marker) and an anti-CD68 antibody (macrophage/microglial marker). The pyramidal and non-pyramidal cells of all three regions analyzed had strong expression of DRD2 and DRD4, whereas DRD3 were very weakly expressed. DRD2 were more strongly expressed in layer III compared to layer V pyramidal neurons. In contrast, DRD4 receptors had a stronger expression in layer V neurons. The most conspicuous finding was the strong expression of DRD2, but not DRD3 or DRD4, receptors in the white matter fibrous astrocytes and in layer I protoplasmic astrocytes. Weak DRD2-immunoreactivity was also observed in protoplasmic astrocytes in layers III and V. These results suggest that DR-expressing astrocytes directly participate in dopaminergic transmission of the human prefrontal cortex.

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