LTP amplitude is not altered after blockade of GABA activity by PICRO injection in the BLA compared with control hippocampal slices. Representative fEPSPs averaged from 10 consecutive stimuli were taken before and after LTP induction at the time points (1 and 2) indicated in the graph. LTP induced in sector CA3 in PICRO-treated rats (•) (a) and sector CA1 (b) does not show significant difference from control (○).

Induction of LTP in the presence of carbachol in rats with a blockade of GABA activity in the BLA shifts synaptic plasticity toward higher amplitude in sectors CA3 and CA1, whereas application of Mc-N-A-343 resulted in a higher level of LTP amplitude only in sector CA3. (a and b) Representative recordings of EPSP amplitudes before and after tetanus delivery. Continuous bath application of carbachol in CA3 (a) and CA1 (b) area increased LTP amplitude in PICRO-treated rats compared with control rats (P = 0.0001). (c) Continuous bath perfusion of Mc-N-A-343 in CA3 area induced potentiation of synaptic plasticity in PICRO-treated rats compared with the low level of plasticity observed in control rats (P = 0.0005). (d) In contrast, area CA1 did not show changes in LTP amplitude between control and PICRO-injected rats with the presence of Mc-N-A-343 in the bath (P = 0.1596). (e) Summary graph of LTP experiments. Data were taken 50 min after high-frequency stimulation, when LTP had stabilized. The groups differed significantly, showing an increase of LTP amplitude (t test, P = 0.0001, P = 0.0005) with carbachol application in CA1 and CA3 area of PICRO-treated rats, whereas bath presence of Mc-N-A-343 induced an elevated level specifically in the CA3 area.

GABA IPSCs evoked by different stimulus intensities showed decreased levels of IPSCs amplitude in both CA3 and CA1 in PICRO-treated rats compared with control rats. (a) Schematic diagram, representing the position of the stimulation (Stim) and recording (Rec) electrodes on a pyramidal neuron stimulated by mossy fibers and inhibited by GABA interneurons. Pyramidal cells, in turn, activate other cells through Schaffer collaterals and their dendrites (Camera lucida drawing of pyramidal neuron and interneurons, courtesy of Duke–Southampton archive http://neuron.duke.edu/cells/cellArchive.html). (b and c) Input/output curves of the GABA IPSCs obtained by recording 10–15 responses averaged for each stimulation intensity tested in CA3 (b) or CA1 (c) areas. The intensity of stimulation was gradually increased from the threshold stimulus determined in each individual experiment, with an increment of 25 μA, to produce IPSCs of increasing amplitude. IPSCs-evoked current exhibited a decreased (P = 0.029) amplitude level in PICRO-treated rats that was higher in CA3 compared with CA1 (P = 0.037). Sample traces of IPSCs (Right) showing unitary responses elicited at 30, 60, and 90 μA stimulus intensity. SL-M, stratum lacunosum moleculare; SR, stratum radiatum; SP, stratum pyramidale; SO, stratum oriens.

GABA spontaneous activity showed decreased amplitude of GABAergic sIPSC but not of frequency in sector CA3 of PICRO-treated rats compared with control rats. (a) Representative traces of consecutive sIPSCs recorded in a pyramidal cell from CA3 area under control conditions (Upper Left) and in PICRO-treated rats (Lower Left). Cumulative-probability-distribution histograms of sIPSC peak amplitude (Right) comparing control with experimental animals. Mean peak amplitude was 49.53 ± 0.15 pA in control rats compared with 24.84 ± 0.23 pA in PICRO-injected rats (P = 0.0009). (b) Bar graph summarizing sIPSCs peak amplitude (Left) and frequency (Right) in PICRO-treated rats compared with control rats in sector CA3. Error bars indicate SEM. (c) A schematic diagram representing the summation of neuronal activity recorded from pyramidal neurons derived from mossy fiber stimulation (positive) and GABAergic interneuron inhibition (negative). Work done in this laboratory (23) has shown that, in PICRO-treated rats, parvalbumin-positive neurons (PVB) contacting the perisomatic region of pyramidal cells and calbindin-D28k (CB) and calretinin (CR)-positive neurons contacting dendritic spines and/or shafts are all decreased compared with SAL-treated rats, whereas cholecystokinin (CCK) terminals are increased on the soma of pyramidal cells in a compensatory manner. SL-M, stratum lacunosum moleculare; SR, stratum radiatum; SP, stratum pyramidale; SO, stratum oriens.