Article Figures & Data
Figures
- Figure 1.
Histology. A–C, Schematic of coronal sections of the rat brain showing representative (for clarity, ∼50%) placements (black circles) of chemotrodes in the mPFC (A), recording electrodes in the NAc (B), and stimulating electrodes in the fimbria (C). The brain sections correspond to the atlas of Paxinos and Watson (1996). The numbers correspond to millimeters from bregma.
- Figure 2.
Inactivation of the mPFC decreases vSub drive of NAc. A, Extracellular recording traces (top) and peristimulus time histograms (bottom; 10 min samples; 300 sweeps) showing a representative example of the inhibitory effect of TTX infusion (1 μm/0.5 μl) into the mPFC on the fimbria-evoked spike probability recorded from a NAc neuron, 10, 20, and 30 min after TTX infusion. The arrows indicate the time at which fimbria is stimulated. B, Mean percentage change (±SEM) of the fimbria-evoked spike probability normalized to the baseline spike probability before tetanus. TTX infusion into the mPFC significantly decreases the fimbria-evoked spike probability of NAc neurons; the attenuation lasts longer than 30 min. *p < 0.05. C, Infusion of dPBS in mPFC had no effect on the fimbria-evoked spike probability of NAc neurons (left panel; n = 8). Infusion of TTX in the motor cortex has no significant effect on the fimbria-evoked spike probability of NAc neurons (middle panel; n = 5), and TTX in the mPFC has no significant effect on the firing rate of NAc neurons (right panel; n = 5).
- Figure 3.
Potentiation of fimbria-evoked spike discharge of NAc neurons circumvents the effects of mPFC inactivation on the vSub–NAc pathway. A, Representative peristimulus time histogram (10 min samples; 300 sweeps) of the induction of LTP into the vSub–NAc pathway 20 and 40 min after tetanic stimulation (20 Hz; 200 pulses; +0.1–0.2 mA to the threshold intensity) of hippocampal afferents. The arrows indicate the time at which the fimbria is stimulated. B, Fimbria-evoked activity is potentiated by tetanic stimulation of the fimbria, and this potentiation lasts longer than 45 min (n = 10). C, Peristimulus time histogram (10 min samples) of representative fimbria-evoked activity recorded from a NAc neuron 20 min after tetanic stimulation and 20 min after TTX infusion into the mPFC. The arrows indicate the time at which the fimbria is stimulated. D, LTP is induced 15 min after the fimbria tetanic stimulation and lasts for 30 min. Enhancement of the evoked activity is not changed by infusion of TTX into the mPFC (NS; n = 16). E, Representative peristimulus time histogram (5 min samples; 150 sweeps) showing inhibitory effect 10 min after TTX infusion (1 μm/0.5 μl) into the mPFC on the fimbria-evoked spike probability recorded from a NAc neuron, and 10 min after tetanic stimulation of the fimbria (F). Tetanic stimulation is only effective in obviating the need for the mPFC if it is delivered before mPFC inactivation, because tetanic stimulation (20 Hz; 10 s; suprathreshold intensity) of the fimbria does not reverse the significant decrease induced by infusion of TTX in the mPFC (n = 6). Error bars indicate SEM. *p < 0.05.
- Figure 4.
Sulpiride blocks the transient attenuation of vSub–NAc drive after tetanic stimulation. A, When displayed on a expanded time base, a significant transient decrease in fimbria-evoked spike probability is revealed immediately after tetanic stimulation and has a duration of ∼1 min (open circle) (n = 36). The arrow indicates the time at which tetanic stimulation and TTX infusion are applied to the fimbria and the mPFC, respectively. B, The transient decrease observed after the tetanic stimulation is blocked by previous systemic administration of sulpiride (5 mg/kg; open circle) (n = 17). The arrow indicates at which time tetanic stimulation is applied to the fimbria. Error bars indicate SEM. *p < 0.05.
- Figure 5.
D2 receptor blockade restores the effects of mPFC inactivation on the vSub–NAc pathway. A, Peristimulus time histogram (5 min samples; 150 sweeps) of a typical response to fimbria stimulation recorded from a NAc neuron 5 min after intravenous sulpiride (5 mg/kg) injection and 20 and 40 min after tetanic stimulation of hippocampal afferents. The arrows indicate the time at which the fimbria is stimulated. B, LTP is induced 10 min after tetanic stimulation of the fimbria and lasts for >35 min (n = 7). C, Peristimulus time histogram (5 min samples) of a typical response to fimbria stimulation recorded from a NAc neuron 5 min after intravenous injection of sulpiride, 20 min after fimbria tetanus, and 20 min after TTX infusion into the mPFC. The arrows indicate the time at which the fimbria is stimulated (n = 9). D, LTP is induced 10 min after fimbria tetanic stimulation. Ten minutes after infusion of TTX into the mPFC, there is a return to baseline spike probability. E, Peristimulus time histogram (5 min samples) of a typical response to fimbria stimulation recorded from a NAc neuron, 10 min after fimbria tetanus, 5 min after intravenous injection of sulpiride, and 10 min after TTX infusion into the mPFC. The arrows indicate the time at which the fimbria is stimulated. F, LTP is induced 15 min after fimbria tetanic stimulation. When intravenous injection of sulpiride is performed after tetanus, no return to baseline spike probability is observed after infusion of TTX in the mPFC (n = 5). Error bars indicate SEM. *p < 0.05.
- Figure 6.
The effects of sulpiride are mediated within the NAc. A, Local application of sulpiride blocks the short-term decrease in spike probability immediately after tetanus of the fimbria. The change in spike probability is sampled every minute for 10 min (5 min before and 5 min after tetanic stimulation). The arrow indicates the time at which tetanic stimulation and TTX infusion are applied to the fimbria and the mPFC, respectively. B, Percentage change in spike probability (5 min samples) recorded after local infusion of sulpiride (3 μg/0.5 μl) into the shell region of the NAc. LTP is induced 10 min after tetanic stimulation of the fimbria. Ten minutes after infusion of TTX into the mPFC, there is a return to baseline spike probability (n = 6). Error bars indicate SEM. *p < 0.05 compared with the baseline; †p < 0.05 compared with the LTP.
- Figure 7.
Schematic illustrating the vSub and the mPFC interactions to the NAc. A, The NAc receives concomitant information from the mPFC and the vSub that are under dynamic regulation of the DA system from the VTA; DA facilitates vSub afferent input via D1 receptors and attenuates mPFC input via D2 receptors. B, Inhibition of the mPFC by TTX attenuates the ability of the vSub to drive spike firing in the NAc. In addition to a direct drive from the vSub, a contribution of the vSub–mPFC–NAc indirect pathway is necessary for the activation of the NAc by the vSub. C, If tetanic stimulation is first applied to the vSub, inactivation of the mPFC fails to affect the vSub–NAc pathway, suggesting that once the vSub–NAc pathway is enhanced via LTP, the mPFC is no longer required to drive spike firing. LTP in the vSub is apparently under the influence of D2 receptors expressed in the accumbens (dashed arrow). D, When the D2 receptor antagonist sulpiride is injected before the tetanic stimulation is applied to the vSub–NAc pathway, inactivation of mPFC reverses the vSub–NAc LTP. This suggests that D2 blockade restored the requirement of an intact vSub–mPFC–NAc pathway to enable direct activation of NAc by the vSub.
