Emergence of GABAergic-dependent regulation of input-specific plasticity in the adult rat prefrontal cortex during adolescence

Abstract

Objective: The prefrontal cortex (PFC) receives multiple cortical and subcortical afferents that regulate higher order cognitive functions, many of which emerge late in adolescence. However, it remains unclear how these afferents influence PFC processing, especially in light of the protracted, late adolescent maturation of prefrontal GABAergic function. Here we investigated the role of PFC GABAergic transmission in regulating plasticity elicited from the ventral hippocampus and basolateral amygdala, and how such modulation undergoes functional changes during adolescence in rats.

Methods: In vivo local field potential recordings, combined with prefrontal microinfusion of the GABA-A receptor antagonist picrotoxin, were employed to study the impact of ventral hippocampal and basolateral amygdala high-frequency stimulation on PFC plasticity.

Results: Ventral hippocampal-induced PFC plasticity begins to appear only by postnatal days (P) 45-55 with a transient suppression of the evoked response. A switch from transient to long-lasting depression (LTD) of the PFC response emerges after P55 and throughout adulthood (P65-120). Recordings conducted in the presence of picrotoxin revealed that PFC GABAergic transmission is critical for the expression of LTD. In contrast, basolateral amygdala stimulation resulted in PFC long-term potentiation, a form of plasticity that is already enabled by P30 and is insensitive to picrotoxin.

Conclusions: The development of ventral hippocampal-dependent PFC LTD is contingent upon the recruitment of local prefrontal GABAergic transmission during adolescence whereas plasticity elicited from the basolateral amygdala is not. Thus, different mechanisms contribute to the refinement of prefrontal plasticity during adolescence as inputs from these two regions are critical for shaping PFC functions.

Figure 1

Age-dependent effects of ventral hippocampal high-frequency stimulation (HFS)-induced plasticity in the medial prefrontal cortex (PFC). (a) Diagram depicting the recording arrangement used to study hippocampal-induced plasticity in the medial PFC by means of local field potential (LFP) recordings. (b) Effects of ventral hippocampal high-frequency stimulation (HFS) on medial PFC LFP in postnatal days (P) 30-40 rats (n=7). Arrows and area marked in gray at 0 minute (min) indicate the HFS period. (c) Effects of ventral hippocampal HFS on medial PFC LFP in P45-55 rats (n=7). (d) Effects of ventral hippocampal HFS on medial PFC LFP in P65-85 rats (n=7). (e) Effects of ventral hippocampal HFS on medial PFC LFP in P95-120 rats (n=7). (f) Bar graph summarizing the mean LFP response from the 30-40 min post-HFS (area marked in gray shown in b, c, d, and e; *p<0.02 vs. P30-40, Tukey post-hoc test). Insets: example traces of ventral hippocampal-evoked LFP before (1) and after (2) HFS (calibration bars: 3 mV, 50 ms).

Figure 2

Role of local prefrontal GABAergic transmission in the regulation of ventral hippocampal-induced plasticity in the medial PFC. (a) Effects of local prefrontal microinfusion of aCSF (n=6) or picrotoxin (n=7) on ventral hippocampal HFS-induced PFC plasticity in the P30-40 age group. (b) Effects of local prefrontal microinfusion of aCSF (n=7) or picrotoxin (n=7) on ventral hippocampal HFS-induced PFC plasticity in the P65-85 age group. (c) Summary of the results shown in a and b. Each dot represents the mean LFP response obtained within the 30-40 min post-HFS (area marked in gray; **p<0.005, ***p<0.0005 vs. P25-40; ⁺⁺⁺p<0.0005 vs. picrotoxin, LSD post-hoc test). (d) Example traces of ventral hippocampal-evoked LFP taken from 5 min pre-HFS (-5) and 35 min post-HFS (+35) illustrating the age-dependent effects of picrotoxin on PFC plasticity (calibration bars: 3 mV, 50 ms). (e) Examples of coronal sections stained with cresyl violet showing the anatomical location of the recording (mPFC: medial PFC) and stimulating (vHC: ventral hippocampus) electrodes from a picrotoxin-infused P65-85 rat. Arrows indicate the track of the electrode placement.

Figure 3

Role of local prefrontal GABAergic function in the regulation of basolateral amygdala-induced plasticity in the medial PFC. (a) Diagram depicting the recording arrangement used to study the effects of basolateral amygdala HFS on medial PFC LFP. (b) Effects of local PFC microinjection of aCSF (n=5) or picrotoxin (n=5) on basolateral amygdala HFS-induced prefrontal LTP in P30-40 rats. (c) Effects of local PFC microinjection of aCSF (n=7) or picrotoxin (n=7) on basolateral amygdala HFS-induced prefrontal LTP in P65-85 rats. (d) Summary of the mean LFP response obtained from the 30-40 min post-basolateral amygdala HFS period (area marked in gray shown in b and c; *p=0.02, main age effect). Insets traces are examples of basolateral amygdala-evoked LFP taken from 5 min pre-HFS (-5) and 35 min post-HFS (+35) illustrating the impact of picrotoxin on PFC plasticity (calibration bars: 3 mV, 50 ms). (e) Examples of cresyl violet-stained coronal sections obtained from a picrotoxin-infused P65-85 rat showing the location of the recording (mPFC: medial PFC) and stimulating (BLA: basolateral amygdala) electrodes. Arrows indicate the track of the electrode placement.