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. 2024 Apr 1;34(4):bhae109.
doi: 10.1093/cercor/bhae109.

Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex

Dominik Kanigowski  1 , Joanna Urban-Ciecko  1
Affiliations

Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex

Dominik Kanigowski et al. Cereb Cortex. .

Abstract

Many studies indicate a broad role of various classes of GABAergic interneurons in the processes related to learning. However, little is known about how the learning process affects intrinsic excitability of specific classes of interneurons in the neocortex. To determine this, we employed a simple model of conditional learning in mice where vibrissae stimulation was used as a conditioned stimulus and a tail shock as an unconditioned one. In vitro whole-cell patch-clamp recordings showed an increase in intrinsic excitability of low-threshold spiking somatostatin-expressing interneurons (SST-INs) in layer 4 (L4) of the somatosensory (barrel) cortex after the conditioning paradigm. In contrast, pseudoconditioning reduced intrinsic excitability of SST-LTS, parvalbumin-expressing interneurons (PV-INs), and vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) with accommodating pattern in L4 of the barrel cortex. In general, increased intrinsic excitability was accompanied by narrowing of action potentials (APs), whereas decreased intrinsic excitability coincided with AP broadening. Altogether, these results show that both conditioning and pseudoconditioning lead to plastic changes in intrinsic excitability of GABAergic interneurons in a cell-specific manner. In this way, changes in intrinsic excitability can be perceived as a common mechanism of learning-induced plasticity in the GABAergic system.

Keywords: VIP interneurons; barrel cortex; in vitro electrophysiology; parvalbumin interneurons; somatostatin interneurons.

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Figures

Fig. 1
Fig. 1
Electrophysiological subtypes of L4 SST-INs in the barrel cortex of Naïve mice. A) Example traces of SST-IN spiking responses and the pie chart showing the distribution of different spiking patterns. B-E) Basic electrophysiological parameters of SST-INs with four different spiking phenotypes. A) Naïve = 31 (16). B-E) LTS = 24 (12), FS = 4 (4), AC = 2 (2), IR = 1 (1).
Fig. 2
Fig. 2
Conditioning increases intrinsic excitability of SST-LTS in L4 of the barrel cortex. A) Examples of cell discharges and B) averaged sigmoidal curves from three groups of mice tested. Both cell discharges and sigmoidal curves reached higher frequencies of APs in the CS + UCS group in comparison to the Naïve and Pseudo groups of mice. C) The curve’s maximum was higher in the CS + UCS group in relation to the Naïve (Kruskal-Wallis test, P ≤ 0.0001; Dunn's test, P = 0.0272) and to the Pseudo groups (Dunn's test, P ≤ 0.0001). D) There were no differences in the steepness of the curves between the groups (Kruskal-Wallis test, P = 0.4258). E) The midpoint was higher in the CS + UCS group compared to the Naïve (Kruskal-Wallis test, P = 0.0011; Dunn's test, P = 0.0028) and the Pseudo groups (Dunn's test, P = 0.0071). F) The discharge adaptation was greater in the Pseudo group than in the Naïve group (One-way ANOVA, F(2, 50) = 4.002, P = 0.0244; Tukey's test, P = 0.0225). B-E) Naïve = 17 (7), CS + UCS = 20 (10), Pseudo = 20 (6). F) Naïve = 16 (6), CS + UCS = 17 (10), Pseudo = 20 (6).
Fig. 3
Fig. 3
Electrophysiological subtypes of L4 PV-INs in the barrel cortex of Naïve mice. A) Example traces and the pie chart of PV-IN spiking patterns. B-E) Basic electrophysiological parameters of PV-INs with FS firing without (FS -reb.) and with (FS +reb.) rebound spikes. No differences were observed in B) resting potential (P = 0.2078); C) input resistance (P = 0.1623); D) rheobase (P = 0.1881); E) maximal frequency of APs (P = 0.3275). A) Naïve = 80 (27). B-E) Unpaired t-test; FS reb. = 23 (10), FS +reb. = 9 (7).
Fig. 4
Fig. 4
Pseudoconditioning decreases intrinsic excitability of PV-INs in L4 of the barrel cortex. A) Cell discharges and B) averaged sigmoidal curves from three groups of mice tested. The cell discharges and the sigmoidal curves present reduced frequencies of APs in the Pseudo group of mice in relation to the Naïve and CS + UCS groups. C) The curve’s maximum was lower in the Pseudo group in comparison to the Naïve (Kruskal-Wallis test, P < 0.0001; Dunn’s test, P < 0.0001) and CS + UCS groups of animals (Dunn’s test, P < 0.0001). D) The curve’s steepness was higher in Pseudo mice in relation to the Naïve (One-way ANOVA, F(2, 88) = 12.24, P < 0.0001; Tukey’s test, P = 0.0001) and CS + UCS groups (Tukey’s test, P < 0.0001). E) No change in the curve’s midpoint was found between groups (One-way ANOVA, F(2, 88) = 1.960, P = 0.1470). F) The discharge adaptation in the Pseudo group was higher in relation to the Naïve (One-way ANOVA, F(2, 84) = 7.769, P = 0.0008; Tukey’s test, P = 0.0008) and CS + UCS groups (Tukey’s test, P = 0.0088). B-E) Naïve = 32 (14), CS + UCS = 34 (11), Pseudo = 25 (10). F) Naïve = 16 (6), CS + UCS = 17 (10), Pseudo = 20 (6).
Fig. 5
Fig. 5
Electrophysiological subtypes of L4 VIP-INs in the barrel cortex of Naïve mice. A) Example traces and the pie chart of four electrophysiological subtypes of VIP-INs in L4 of the barrel cortex. B-E) The comparison of basic electrophysiological properties between VIP-INs presenting AC or LTS spiking pattern. B) The resting potential was depolarized in VIP-LTS in comparison to VIP-AC (P = 0.0425). C) The input resistance was similar between the firing subtypes (P = 0.3405). D) The rheobase was higher in VIP-AC than VIP-LTS (P = 0.0204). E) There were no differences in the maximal frequency of APs between the two subtypes of interneurons (P = 0.8714). A) Naïve = 62 (31). B, C, E) Unpaired t-test; AC = 18 (13), LTS = 15 (10). D) Mann-Whitney test; AC = 17 (12), LTS = 15 (10).
Fig. 6
Fig. 6
Intrinsic excitability of VIP-AC differs between conditioned and pseudoconditioned groups of mice. A, B) The CS + UCS and Pseudo groups vary in the AP frequency, as shown by A) the examples of firing responses as well as by B) averaged sigmoidal curves. C) The maximal frequency of APs was decreased in the Pseudo group in contrast to the CS + UCS mice (One-way ANOVA, F(2, 63) = 7.431, P = 0.0013; Tukey’s test, P = 0.0009), but not the Naïve mice. D) The curve’s steepness was comparable between groups (One-way ANOVA, F(2, 63) = 0.8808, P = 0.4195). E) The curve’s midpoint did not differ between groups (Kruskal-Wallis test, P = 0.9813). F) The spike adaptation was lower in the CS + UCS group relative to the Naïve group (One-way ANOVA, F(2, 62) = 3.670, P = 0.0312; Tukey’s test, P = 0.0234). B-E) Naïve = 16 (11), CS + UCS = 17 (10), Pseudo = 33 (20). F) Naïve = 16 (11), CS + UCS = 16 (10), Pseudo = 33 (20).
Fig. 7
Fig. 7
Conditioning and pseudoconditioning do not influence intrinsic excitability of L4 VIP-LTS. A) Examples of cell discharges and B) sigmoidal curves in tested groups of mice. C-F) No differences were observed in C) the curve’s maximum (Kruskal-Wallis test, P = 0.3091); D) the curve’s steepness (One-way ANOVA, F(2, 36) = 1.800, P = 0.1799); E) the curve’s midpoint (One-way ANOVA, F(2, 36) = 1.099, P = 0.3442); F) spike adaptation (One-way ANOVA, F(2, 34) = 0.0016, P = 0.9984). B-E) Naïve = 13 (8), CS + UCS = 9 (8), Pseudo = 17 (17). F) Naïve = 12 (8), CS + UCS = 8 (7), Pseudo = 17 (17).
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