Figure 1.
AP firing rate is decreased while AHP is increased in SO of CA2/3 fast–spiking interneurons of PICRO-treated rats in the presence of kainic acid (KA).
Application of KA does not affect duration (A) or RMP (B) in PICRO-treated rats compared to experimental conditions with no drug. In contrast, AHP is increased (C) and AP firing rate is decreased in PICRO rats compared with saline–infused animals in the presence of KA (D, E). Insets in C, E show representative traces of interneuron AP responses from SAL (on the left) and PICRO (on the right) infused animals. F, Plot of instantaneous firing frequency versus time for spikes elicited by single current steps during the first 500 ms of a 1s current pulse in slices from PICRO rats with or without KA in the external solution. * p = <0.05 or ***p<0.001. Error bars indicate SEM.
Table 1.
I/R values of SO-CA2/3 FS-Interneurons in SAL and PICRO- Treated Rats.
Figure 2.
Increased AHP Amplitude and decreased AP firing in the presence of kainic acid is dependent on the GluR5 subunit.
A, Bath application of UBP296 does not change AP duration and RMP (B) of fast-spiking interneurons from PICRO-treated rats compared to experimental conditions with no drug. C, D, UBP296 application is associated with an increase of AHP and decrease of AP firing rate in SO of CA2/3 fast-spiking interneurons from PICRO-treated rats. A significant increase of AHP amplitude has been observed when comparing SAL+KA+UBP296 versus PICRO+KA+UBP296 groups (p<0.001). UBP296 failed to induce any electrophysiological changes in control rats (A–E). E, This panel shows representative traces recorded before and after application of UBP296 in PICRO versus SAL rats. Results are presented as the mean ± SEM. *p<0.05 or ***p<0.001 versus saline.
Figure 3.
The reduced responsiveness of fast-spiking interneurons from PICRO-treated rats to KA is mediated by GluR6/7 subunit-containing KARs.
The GluR6/7 receptor antagonist (NS102) does not have a significant effect on duration (A), RMP (B), AHP (C) or AP frequency (D, E) in SO CA2/3 fast-spiking interneurons from PICRO- infused rats compared to conditions with no drug application. E, Right side of the panel shows representative traces recorded with and without NS102 in the external solution. F, AP spike frequency after NS102 bath perfusion compared to SAL with KA (the plot showing the SAL with KA data is the same as in Figure 1D) (ANOVA: p = 0.0001). *p<0.05 or **p<0.01. Error bars are SEM.
Figure 4.
Decrease of AP frequency in the presence of KA in SO CA2/3 fast-spiking interneurons PICRO–treated rats is partially relieved by the blockade of GABA receptors.
A, The GABAA and GABAB antagonists picrotoxin and CGP55845, respectively, induced a significant increase of AP frequency compared to recordings with KA only application (PICRO+KA plot here is the same as in Figure 1D) (ANOVA: p = 0.05, n = 7) (see red labeled symbol). It also resulted in a decrease in AHP (C). B, Representative traces recorded in slices from PICRO-treated rats (left) with KA (middle) and CGP55845 with picrotoxin (right) in the external solution. **p<0.01. Error bars are SEM.
Figure 5.
ZD7288 reverses the increase of AP frequency induced by CGP55845 with picrotoxin in SO CA2/3 fast-spiking interneurons PICRO–treated rats.
A, B, Application of the Ih blocker ZD7288 significantly decreases AP frequency and increases duration (C) compared to recordings with CGP55845 (GABAB antagonist) and picrotoxin (GABAA antagonist) (the red labeled plot is the same as in Figure 4E) bath application (ANOVA: p = 0.02, n = 6). In contrast, bath perfusion of tertiapin-Q did not have a significant effect on interneuronal electrophysiological properties (A, B, C). Traces on the bottom of the panel were recorded with the application of KA and GABAA,B blockers (left), tertiapin-Q- (middle) and ZD7288 (right). ***p<0.001. Error bars are SEM.
Figure 6.
A schematic diagram depicting how an increase of excitatory activity from the BLA might influence the interaction of inhibitory and disinhibitory GABA cells in the SO of CA2/3.
The results reported in this study can be best explained by a model in which BLA afferents influence two types of interneurons: one that is a fast–spiking (FS) inhibitory cell (red) and one that is a disinhibitory neuron (green) that forms GABA-to-GABA interactions with the FS interneuron (1). The diagram suggests that BLA fibers may provide two different KARs-mediated glutamatergic interactions with the disinhibitory neuron. Because PICRO-infused rats showed a significant increase in the amplitude of AHPs in FS-cells, these glutamatergic fibers probably stimulate the KARs located in dendrites of disinhibitory neuron through axodendritic connections (2). Additionally, the further increase in the amplitude of AHPs recorded in FS cells observed in PICRO-treated rats with blockade of the GluR5 subunits of KARs suggests that BLA fibers may also provide a pre-synaptic inhibitory effect of the dysinhibitory axon terminal synapting on the FS cells. This last effect is mediated by GluR5 or 6/7 on GABA-to-GABA terminals (3). BLA fibers have been found to form axo-axonic connections in cortical neuropil (Cunningham et al. 2002) and, in the SO of CA2/3, similar connections with the axon terminations of disinhibitory interneurons maybe present. This circuitry model provides new insights as to how BLA fibers may contribute to the synchronization of oscillatory rhythms generated in the amygdala and hippocampus during normal and abnormal cognitive states.