Electrophysiological evidence of mediolateral functional dichotomy in the rat nucleus accumbens during cocaine self-administration II: phasic firing patterns

Abstract

In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self-administration sessions are differentially distributed in the NAcc, rats were implanted with jugular catheters and microwire arrays in different NAcc subregions (core, dorsal shell, ventromedial shell, ventrolateral shell, or rostral pole). Neural recording sessions were typically conducted on days 13-17 of cocaine self-administration (0.77 mg/kg per 0.2-mL infusion; fixed-ratio 1 schedule of reinforcement; 6-h daily sessions). Pre-press rapid phasic firing rate changes were greater in lateral accumbal (core and ventrolateral shell) than in medial accumbal (dorsal shell and rostral pole shell) subregions. Slow phasic pattern analysis revealed that reversal latencies of neurons that exhibited change + reversal patterns differed mediolaterally: medial NAcc neurons exhibited more early reversals and fewer progressive/late reversals than lateral NAcc neurons. Comparisons of firing patterns within individual neurons across time bases indicated that lateral NAcc pre-press rapid phasic increases were correlated with tonic increases. Tonic decreases were correlated with slow phasic patterns in individual medial NAcc neurons, indicative of greater pharmacological sensitivity of neurons in this region. On the other hand, the bias of the lateral NAcc towards increased pre-press rapid phasic activity, coupled with a greater prevalence of tonic increase firing, may reflect particular sensitivity of these neurons to excitatory afferent signaling and perhaps differential pharmacological influences on firing rates between regions.

Figure 1

Examples of slow phasic reversal firing patterns. Each peri-event time histogram (PETH) displays the firing pattern of one neuron during the minutes before and after the lever press. The ordinate of each histogram displays the average firing rate (i.e. average discharges/s calculated as a function of 0.1-min bins). Time 0 (vertical dashed line) on the abscissa marks the occurrence of the cocaine-reinforced lever press. (A) Examples of decrease + progressive reversal firing patterns. (B) Examples of other categories of slow phasic patterns. Top, increase + progressive reversal; middle, increase + early reversal; bottom, decrease + early reversal. For each PETH, the inset depicts the corresponding neural waveform. Calibrations (bars in A, top) of waveforms: 0.25 ms, 0.10 mV (top left waveform); 0.25 ms, 0.20 mV (all other waveforms).

Figure 2

Mediolateral comparison of slow phasic reversal categories. Neurons that were histologically confirmed to be in either the lateral nucleus accumbens (NAcc) (i.e. core\ventrolateral shell; n = 74) or the medial NAcc (i.e. dorsal shell\rostral pole shell; n = 17) were evaluated in terms of whether they exhibited: (i) progressive or late reversal patterns (n = 32); or (ii) early reversal patterns (n = 14). To determine whether reversal categories are differentially expressed in the NAcc, a chi-square analysis was conducted. The percentage of early-reversing neurons was greater in the medial NAcc, whereas progressive/late-reversing neurons were more prevalent in the lateral NAcc [χ²(exact) = 4.70, degrees of freedom = 1, *P < 0.05). A post hoc odds ratio analysis confirmed that the differential probability of observing the two different reversal categories between regions was significant (oddsPLR/oddsER = 5.37, *P < 0.05). PLR, progressive/late-reversing; ER, early-reversing; D, dorsal; RP, rostral pole; VL, ventrolateral

Figure 3

Examples of rapid phasic firing patterns. Each peri-event time histogram displays the firing pattern of a different neuron during the seconds before and after the lever press. The ordinate of each histogram displays average firing rate (i.e. average discharges/s calculated as a function of 0.2-s bins). Time 0 (vertical dashed line) on the abscissa marks the occurrence of the cocaine-reinforced lever press, and corresponds with the raster display above it. (A) A pre-press firing rate increase. (B) A lever press increase. (C) A post-press increase. (D) A lever press decrease. Insets depict corresponding neural waveforms. Calibrations (bars in A) of waveforms: insets A, B, and C, 0.25 ms, 0.20 mV; inset D, 0.25 ms, 0.15 mV

Figure 4

Frequency distributions of pre-press (left panel) and post-press (right panel) rapid phasic firing rate change magnitudes in the medial nucleus accumbens (M-NAcc) vs. the lateral NAcc (L-NAcc). The magnitude of firing rate change is expressed as B/(A + B) (bottom side of x-axis). Values from 0.49 to 0 and from 0.51 to 1.00 reflect increasingly larger firing rate decreases and increases, respectively. Values of 0.50 reflect no change from baseline firing rate (vertical dashed line). The top side of the x-axis indicates twofold, fourfold, etc. increases above, or decreases below, baseline firing rate values. The ordinate scale indicates percentages of the total neurons in the medial (N = 17) and lateral (N = 74) NAcc. The distribution of pre-press B/A + B increases was greater in lateral NAcc (core/ventrolateral shell) neurons than in medial NAcc (dorsal shell/rostral pole shell) neurons [t₂₆ = 1.71, P = 0.02).

Figure 5

Tonic firing changes in neurons that exhibit slow phasic firing patterns are differentially expressed among nucleus accumbens (NAcc) subregions. The graph depicts tonic firing data for neurons that exhibited slow phasic firing changes. Symbols indicate subregional placement of histologically confirmed NAcc microwires (see key). B/A + B values from 0.49 to 0 and from 0.51 to 1.00 reflect increasingly larger firing rate decreases and increases, respectively. A rather broad distribution of increases and decreases of slow phasic and tonic firing magnitudes is revealed for lateral NAcc neurons (e.g. core and ventrolateral shell), including opposite signs in firing rate change between time bases (i.e. symbols in upper left and lower right quadrants). For the medial NAcc (i.e. dorsal shell and rostral pole shell) and dorsal border regions, it is notable that slow phasic changes were exclusively decreases in neurons that also exhibited tonic decreases (lower left quadrant). D, dorsal; VL, ventrolateral; RP, rostral pole; V, ventral.

Figure 6

Percentage of slow phasic (SP) increases and SP decreases among tonic categories. All tonic neurons (n = 135) were evaluated by category (increase, decrease, and non-responsive) for the prevalence of SP increases and decreases within them. SP decreases were observed in 33% of tonic increase neurons, 44% of tonic decrease neurons, and 43% of no tonic change neurons. SP increases were observed in 43% of tonic increase neurons, 2% of tonic decrease neurons, and 8% of no tonic change neurons. A 2 × 3 chi-square test revealed that SP increase and decrease reversal patterns were differentially expressed across tonic categories [χ²(2) = 17.3338, P < 0.001). An odds ratio analysis confirmed a differential prevalence of SP increase and decrease patterns between the tonic increase and decrease categories: odds ratio (95% confidence interval) = 0.0311 (0.0033–0.2892).