Neurons In Rat Frontal Cortex Research Articles

Distribution patterns of corticocortical and thalamocortical excitatory inputs onto neocortical neurons in rat frontal cortex

Distribution patterns of corticocortical and thalamocortical excitatory inputs onto neocortical neurons in rat frontal cortex

Effects of chronic exposure to desipramine and mianserin on Ca2+ mobilization induced by noradrenaline, acetylcholine, and high K+ in rat frontocortical neurons.

We examined the chronic effects of desipramine and mianserin on increases of intracellular Ca2+ concentration ([Ca2+]i) induced by noradrenaline (NA), acetylcholine (ACh), or high K+ in cultured neurons of rat frontal cortex, using fluoromicroscopic analysis with Ca(2+)-sensitive dye fura-2. NA- and ACh-induced [Ca2+]i increases were abolished in the presence of 1 microM prazosin and 1 microM atropine, respectively, and partially inhibited in the absence of extracellular Ca2+. When cultures were treated with 1 microM desipramine for 5 days, the dose-dependent curves of NA- and ACh-induced (0.01-100 microM) [Ca2+]i increases were similar to those of the control cultures. Neither NA- nor ACh-induced [Ca2+]i increases were affected by desipramine exposure, even at a concentration of 10 microM. Treatment with mianserin (0.1, 1, or 10 microM) for 5 days had no effect on either NA- or ACh-induced [Ca2+]i increases. Additionally, [Ca2+]i increases induced by high K+ (12.5-50 mM) were not affected following chronic 10 microM desipramine exposure for 5 days. Thus, chronic antidepressant exposure does not modify the [Ca2+]i increased mediated by alpha 1-adrenoceptors, muscarinic cholinergic receptors, or voltage-sensitive Ca2+ channels. Changes in Ca2+ mobilization may not be one of the mechanisms of antidepressants.

Imipramine stimulates phospholipase C activity in rat brain

We previously demonstrated that antidepressant drugs (ADs) cause Ca 2+ release from inositol 1,4,5-trisphosphate-sensitive Ca 2+ stores in cultured neurons of rat frontal cortex. The present study examines the mechanism by which tricyclic ADs activate phospholipase C (PLC) in rat frontal cortex. Using an exogenous substrate to measure PLC activity, we demonstrated that a tricyclic AD, imipramine, stimulated PLC activity of the frontal cortex membrane in a concentration-dependent manner. Two tricyclic ADs, desipramine and amitriptyline, also stimulated PLC activity, while Li + or pargyline had no effect on PLC activity. Although imipramine did not activate PLC in the membrane in the absence of Ca 2+, imipramine synergistically activated PLC in the presence of Ca 2+. This result indicates that the mechanism of PLC activation by imipramine is different from its activation by Ca 2+. Imipramine stimulated PLC activity in the cytosol of rat frontal cortex as well as in the membrane. Preincubation of the cytosol with anti-PLC- β 1 antibody prevented the imipramine-mediated activation of PLC. However, preincubation with anti-PLC- γ 1 or anti-PLC- δ 1 did not prevent activation of PLC. These results suggest that imipramine activates PLC- β 1 directly without receptor or guanine nucleotide binding protein mediation.

Analysis of synaptic inputs and targets of physiologically characterized neurons in rat frontal cortex: Combined in vivo intracellular recording and immunolabeling

Ultrastructural immunocytochemical identification of transmitters in afferent terminals and targets of individual physiologically characterized neurons is essential for understanding the complex circuitry within the mammalian neocortex. For this type of analysis, we examined the utility of combining in vivo intracellular recording and biocytin injections with silver intensified 1 nm immunogold labeling of GABA and the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH). These transmitters are found to local neurons and afferents known to prominently modulate the activity of pyramidal neurons in the neocortex. Individual neurons were physiologically characterized and filled with biocytin in the frontal cortex of anesthetized rats. The brains were then preserved by vascular perfusion with aldehydes. Single vibratome sections through the recording site were reacted (1) for immunoperoxidase detection of biocytin and (2) for immunogold labeling of GABA or TH. Dually labeled sections were processed for light microscopy or embedded in plastic for electron microscopy. The dense peroxidase product for biocytin was detected in pyramidal neurons. These were located in superficial as well as deep cortical laminae, and were readily distinguished from immunogold silver labeling. GABA labeled terminals formed symmetric synapses with larger biocytin filled dendrites, whereas the TH labeled terminals contacted distal dendrites and spines. Peroxidase labeling for biocytin also was seen in a few axon terminals forming synapses with unlabeled and with GABA immunoreactive dendrites. These results suggest that single pyramidal neurons of the rat frontal cortex receive dual input from both GABA and catecholamine terminals. Additionally, this study demonstrates the usefulness of silver enhancement of 1 nm colloidal gold prior to plastic embedding for electron microscopic detection of neurotransmitters within afferents and targets of neurons physiologically characterized in vivo.

Ca2+ Release from Inositol 1,4,5‐Trisphosphate‐Sensitive Ca2+ Store by Antidepressant Drugs in Cultured Neurons of Rat Frontal Cortex

The ability of antidepressant drugs (ADs) to increase the concentration of intracellular Ca2+ ([Ca2+]i) was examined in primary cultured neurons from rat frontal cortices using the Ca(2+)-sensitive fluorescent indicator fura-2. Amitriptyline, imipramine, desipramine, and mianserin elicited transient increases in [Ca2+]i in a concentration-dependent manner (100 microM to 1 mM). These four AD-induced [Ca2+]i increases were not altered by the absence of external Ca2+ or by the presence of La3+ (30 microM), suggesting that these ADs provoked intracellular Ca2+ mobilization rather than Ca2+ influx. All four ADs increased inositol 1,4,5-trisphosphate (IP3) contents by 20-60% in the cultured cells. The potency of the IP3 production by these ADs closely correlated with the AD-induced [Ca2+]i responses. Pretreatment with neomycin, an inhibitor of IP3 generation, significantly inhibited amitriptyline- and imipramine-induced [Ca2+]i increases. In addition, by initially perfusing with bradykinin (10 microM) or acetylcholine (10 microM), which can stimulate the IP3 generation and mobilize the intracellular Ca2+, the amitriptyline responses were decreased by 76% and 69%, respectively. The amitriptyline-induced [Ca2+]i increases were unaffected by treatment with pertussis toxin. We conclude that high concentrations of amitriptyline and three other ADs mobilize Ca2+ from IP3-sensitive Ca2+ stores and that the responses are pertussis toxin-insensitive. However, it seems unlikely that the effects requiring high concentrations of ADs are related to the therapeutic action.

Event-related slow potentials and activity of singly neurons in rat frontal cortex.

Event-related slow potentials and single unit activity were recorded from frontal cortex of unanesthetized, restrained rats trained to associate an auditory cue with rewarding medial forebrain bundle (MFB) stimulation. The majority of cortical units demonstrated an alteration of firing rate after the cue, with the predominant response being excitatory. The patterns of unit response during the interval between the cue and reinforcement varied considerable and few units showed a pattern which coincided temporally with the wave forms of the negative slow potential responses. These results indicate that negative cortical slow potential responses to meaningful stimuli are associated with an overall increase in activity of cortical neurons.