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

Abstract

Given the increasing research emphasis on putative accumbal functional compartmentation, we sought to determine whether neurons that demonstrate changes in tonic firing rate during cocaine self-administration are differentially distributed across subregions of the NAcc. Rats were implanted with jugular catheters and microwire arrays targeting NAcc subregions (core, dorsal shell, ventromedial shell, ventrolateral shell and rostral pole shell). Recordings were obtained after acquisition of stable cocaine self-administration (0.77 mg/kg/0.2mL infusion; fixed-ratio 1 schedule of reinforcement; 6-h daily sessions). During the self-administration phase of the experiment, neurons demonstrated either: (i) tonic suppression (or decrease); (ii) tonic activation (or increase); or (iii) no tonic change in firing rate with respect to rates of firing during pre- and post-drug phases. Consistent with earlier observations, tonic decrease was the predominant firing pattern observed. Differences in the prevalence of tonic increase firing were observed between the core and the dorsal shell and dorsal shell-core border regions, with the latter two areas exhibiting a virtual absence of tonic increases. Tonic suppression was exhibited to a greater extent by the dorsal shell-core border region relative to the core. These differences could reflect distinct subregional afferent processing and/or differential sensitivity of subpopulations of NAcc neurons to cocaine. Ventrolateral shell firing topographies resembled those of core neurons. Taken together, these observations are consistent with an emerging body of literature that differentiates the accumbens mediolaterally and further advances the likelihood that distinct functions are subserved by NAcc subregions in appetitive processing.

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).