Prelimbic and infralimbic neurons signal distinct aspects of appetitive instrumental behavior

Abstract

It is thought that discrete subregions of the medial prefrontal cortex (mPFC) regulate different aspects of appetitive behavior, however, physiological support for this hypothesis has been lacking. In the present study, we used multichannel single-unit recording to compare the response of neurons in the prelimbic (PL) and infralimbic (IL) subregions of the mPFC, in rats pressing a lever to obtain sucrose pellets on a variable interval schedule of reinforcement (VI-60). Approximately 25% of neurons in both structures exhibited prominent excitatory responses during rewarded, but not unrewarded, lever presses. The time courses of reward responses in PL and IL, however, were markedly different. Most PL neurons exhibited fast and transient responses at the delivery of sucrose pellets, whereas most IL neurons exhibited delayed and prolonged responses associated with the collection of earned sucrose pellets. We further examined the functional significance of reward responses in IL and PL with local pharmacological inactivation. IL inactivation significantly delayed the collection of earned sucrose pellets, whereas PL inactivation produced no discernible effects. These findings support the hypothesis that PL and IL signal distinct aspects of appetitive behavior, and suggest that IL signaling facilitates reward collection.

Figure 1. PL and IL exhibited temporally distinct reward responses.

A, Neuronal activity was recorded from PL or IL while rats pressed a lever for sucrose pellets on a variable interval schedule of reinforcement of 60 seconds (VI-60). The lever and food dish were 6 cm apart from each other, and a rewarded press resulted in only one sucrose pellet. B, Coronal reconstruction of recording sites (bregma +2.80 mm). Dots represent the position of electrode tips, and activity was recorded from a total of 244 neurons from 28 rats (PL: n = 134, IL: n = 110). C, Average normalized response of PL and IL during rewarded presses (all recorded neurons included). PL exhibited a fast and transient response that lasted for a few hundred milliseconds, whereas IL exhibited a response of longer latency that lasted for several seconds. D, Neither structure responded during unrewarded presses. [Data is illustrated as z-scores, in 100-ms bins. Error in all figures represents SEM.].

Figure 2. Transiently-responsive neurons predominated in PL, whereas prolonged-responsive neurons predominated in IL.

A-B, Single-neuron examples of transient and prolonged excitatory responses during rewarded lever presses. Insets show the activity of these neurons during unrewarded presses, and gray boxes represent the temporal windows used to quantify the proportion of neurons showing each type of response. C, Percentage of neurons per structure that showed either transient or prolonged excitation during rewarded lever presses. PL exhibited significantly more transiently-responsive neurons than IL, whereas IL exhibited significantly more prolonged-responsive neurons than PL (Χ² tests: **p<0.01).

Figure 3. Latencies for PL, IL, and reward collection.

The distribution of PL latencies peaked at ∼0.1 s after rewarded lever presses were achieved (A), whereas the distribution of IL latencies peaked at ∼1 s (B). Similar to IL, the distribution of latencies for reward collection peaked at ∼1 s after rewarded presses were achieved (C).

Figure 4. Inactivation of IL, but not PL, altered the time course of reward collection.

Either the GABA_A agonist muscimol (Mus) or saline vehicle (Sal) was bilaterally infused into IL or PL 30 min prior to testing animals on VI-60. A–B, Inactivation of IL, but not PL, significantly delayed the collection of earned pellets (**p<0.01, compared to all other groups). C–E, Other behavioral measures were unaffected by IL or PL inactivation, including the rate of lever pressing (C), latency for the resumption of lever pressing after collecting the earned pellets (D), or general locomotion in an open-field test (E). [Inset in B shows the location of injector tips. PL-Sal: n = 6, PL-Mus: n = 6, IL-Sal: n = 4, IL-Mus: n = 6].