The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons - PubMed (original) (raw)

The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons

D J Lodge et al. Proc Natl Acad Sci U S A. 2006.

Abstract

In response to behaviorally salient stimuli, dopamine (DA) neurons fire in bursts. Burst firing induces a large transient increase in synaptic DA and is regarded as the functionally relevant mode of transmission that signals reward and modulates goal-directed behavior. DA neuron burst firing is dynamically regulated by afferent inputs, and it is not present in vitro because of severing of afferent processes. However, what afferents are requisite for burst firing in vivo is not known. Here, we show that tonic input from the laterodorsal tegmental nucleus (LDTg) is required for glutamate-elicited burst firing in ventral tegmental area DA neurons of anesthetized rats. Also, after LDTg inactivation, DA neurons fire as they do in vitro (i.e., as pacemakers); even direct glutamate application fails to cause them to burst fire under these conditions. These data show that the LDTg is critical to normal DA function, and thus, pathology within this region may lead to aberrant DA signaling.

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Conflict of interest statement

Conflict of interest statement: No conflicts declared.

Figures

Fig. 1.

Localization of cannula placements throughout the PPTg and LDTg. The shaded area represents the range of intracranial cannula tip placements. Numbers beside each plate represent the approximate A/P distance from bregma.

Fig. 2.

LDTg manipulations alter the activity states of VTA DA neurons. NMDA (0.75 μg per 0.5 μl), baclofen/muscimol (0.2 μg each per 0.5 μl), carbachol (4 μg per 0.5 μl), scopolamine (50 μg per 0.5 μl), or vehicle (Dulbecco's PBS) were injected into the LDTg, and the activity of spontaneously active VTA DA neurons was examined. (A_–_C) The following three parameters of activity were recorded: population activity (number of spontaneously firing DA neurons per electrode track) (A), average firing rate (B), and average percentage of spikes fired in bursts (C). LDTg activation was found to increase population activity without affecting firing rate or burst firing; however, inactivation of the LDTg decreased firing rate and potently attenuated burst firing. (D) Activation of the PPTg by NMDA, which was found previously to potently increase burst firing, failed to alter any of these parameters after LDTg inactivation (filled bars) compared with LDTg inactivation alone (open bars). Horizontal lines represent control (vehicle infusions). ∗, P < 0.05, compared with control (vehicle infusions) by one-way ANOVA (Holm–Sidak post hoc test; n = 6 rats per group).

Fig. 3.

Inactivation of the LDTg by baclofen/muscimol causes a regularization in the firing pattern of DA neurons recorded in the VTA. (A_–_C) In the control, DA neurons recorded in vivo typically display an irregular spontaneous firing pattern (A), as shown by the variable ISI histogram (B) and lack of peaks in the corresponding autocorrelogram (C). (D_–_F) After baclofen/muscimol inactivation of the LDTg, DA cells display a pattern of activity that is not usually observed in vivo, which is a significantly more regular, pacemaker-like pattern (D), as shown by a uniform distribution of the ISI histogram (E) and regularly occurring peaks in the autocorrelogram (F).

Fig. 4.

Glutamate-induced burst firing is not present after LDTg inactivation. (A and B) Microiontophoretically applied glutamate resulted in a current-related increase in DA neuron firing rate (A) and burst firing (B) in control rats. (C and D) After LDTg inactivation by baclofen/muscimol, glutamate increased DA neuron firing rate (C) but did not significantly alter burst firing in most neurons (D). (E and F) Histograms represent group data from control (n = 6 rats; 10 cells) and LDTg-inactivated (n = 11 rats; 23 of 26 cells) rats, showing the effect of glutamate on average firing rate (E) or burst firing (F) before (open bars) and during (filled bars) glutamate microiontophoresis (−10 nA current). †, P < 0.05, compared with baseline, by paired t test.

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The laterodorsal tegmentum is essential for burst firing of ventral tegmental area dopamine neurons - PubMed (original) (raw)