Effect of disconnecting the orbital prefrontal cortex from the nucleus accumbens core on inter-temporal choice behaviour: a quantitative analysis

Abstract

Previous experiments showed that destruction of the orbital prefrontal cortex (OPFC) or the nucleus accumbens core (AcbC) in rats altered choice between two delayed food reinforcers. Application of a quantitative model of inter-temporal choice suggested that lesions of either structure increased the delay-dependent degradation of reinforcer value (delay discounting); destruction of the OPFC (but not the AcbC) also increased the relative value of the larger reinforcer. This experiment examined the effect of disconnecting the OPFC from the AcbC on inter-temporal choice. Rats received excitotoxin-induced contralateral lesions of the OPFC and AcbC (disconnection), severing of the anterior corpus callosum (callosotomy), a combined lesion (disconnection+callosotomy) or sham lesions. They were trained in a discrete-trials progressive delay schedule to press levers A and B for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after a delay d(B). d(B) increased across blocks of trials; d(A) was manipulated across phases of the experiment. Indifference delay, d(B50) (value of d(B) corresponding to 50% choice of B), was estimated for each rat in each phase, and linear indifference functions (d(B50)vs. d(A)) were derived. The disconnection+callosotomy group showed a lower intercept of the indifference function (implying a higher rate of delay discounting) than the sham-lesioned group; the disconnection group showed a similar but less robust effect, whereas the callosotomy group did not differ significantly from the sham-lesioned group. The results suggest that OPFC-AcbC connections are involved in delay discounting of food reinforcers, but provide no evidence for an involvement of OPFC-AcbC connections in regulating sensitivity to reinforcer size.

Fig. 1

Group mean data from the sham-lesioned (top row), disconnection (second row), callosotomy (third row) and disconnection + callosotomy (bottom row) groups. Left-hand panels show preference functions (percent responding on lever B, %B, vs. delay to the larger of the two reinforcers after a response on B, d_B, s). Each set of points shows data collected from one phase of the experiment, in which the delay to the smaller reinforcer (d_A) was set at the value indicated (see inset). The horizontal reference line denotes indifference (%B = 50). The intersection between each preference function and the indifference level denotes the indifference delay (d_B(50)) for that phase. Right-hand panels show transformations of the preference functions with d_B (s) on a logarithmic scale, and fitted logistic psychophysical functions, for each value of d_A.

Fig. 2

Linear indifference functions obtained for the sham-lesioned (white circles), disconnection (grey circles), callosotomy (grey triangles) and disconnection + callosotomy (black circles) groups. Ordinate: indifference delay to the larger reinforcer (d_B(50), s); abscissa: imposed delay to the smaller reinforcer (d_A, s). Points show group mean data; vertical bars indicate S.E.M.s for the sham-lesioned and disconnection + callosotomy groups; lines are best-fit linear functions (see inset for the equations and goodness-of-fit of the fitted functions).

Fig. 3

Parameters of the linear indifference functions from individual rats in the sham-lesioned (unshaded), callosotomy (cross-hatched), disconnection (horizontally shaded) and disconnection + callosotomy (black) groups. Columns show group mean values, vertical bars indicate S.E.M.s. Left-hand panel: slope of linear function; right-hand panel: intercept of linear function. Significant main effect of disconnection lesion: ^#P < 0.05; significant difference from sham-lesioned group: *P < 0.05 (see text for details).

Fig. 4

Weber fraction (left-hand panel) and slope parameter (right-hand panel) derived from psychophysical analysis of preference functions (see right-hand panels in Fig. 1). See text for derivation of the Weber fraction. Columns show group mean data; vertical bars indicate S.E.M.s; conventions as in Fig. 3.

Fig. 5

Photomicrographs showing examples of the lesions. (A–D) OPFC. (A) cresyl violet stained coronal section from a sham-lesioned rat; (B) section stained for NeuN. (C and D) corresponding sections showing quinolinic acid-induced lesion of the OPFC. Note the area of gliosis and neuronal loss in the OPFC. (E–H) Nucleus accumbens core (AcbC). (E and F): cresyl violet- and NeuN-stained sections from a sham-lesioned rat. (G and H) corresponding sections showing quinolinic acid-induced lesion of the AcbC. Note ventricular dilatation and neuronal loss. White broken lines in (A) and (E) show approximate extent of the OPFC and AcbC in the sham-lesioned rat. (I) Callosotomy: cresyl violet-stained section from a lesioned rat. Note the destruction of the corpus callosum, with attendant ventricular dilatation and damage to mesial surface of overlying cortex. LV: lateral ventricle; aca: anterior commissure (anterior portion); CC: corpus callosum.