Modulation of basolateral amygdala neuronal firing and afferent drive by dopamine receptor activation in vivo

Abstract

The basolateral amygdala (BLA) is implicated in responding to affective stimuli. Dopamine (DA) is released in the BLA during numerous conditions; however, the neurophysiological effects of DA in the BLA have not been examined in depth. In this study, the effects of DA receptor manipulation on spontaneous and afferent-driven neuronal firing were examined using in vivo extracellular single-unit recordings in parallel with systemic and iontophoretic drug application, and stimulation of the substantia nigra/ventral tegmental area in the rat. The effects of DA receptor activation in the BLA were found to depend on the characteristics of the BLA neuron examined, causing an increase in the firing rate of putative interneurons and a decrease in the firing of identified projection neurons. Additionally, DA receptor activation attenuated short-latency spikes evoked by electrical stimulation of prefrontal cortical and mediodorsal thalamic inputs to the BLA while potentiating the responses evoked by electrical stimulation of sensory association cortex. DA receptor activation can thus attenuate BLA projection neuron firing via two mechanisms: (1) by a direct inhibition, and (2) by indirect actions mediated via activation of BLA interneurons. This is hypothesized to lead to a global filtration of weaker inputs. Moreover, DA potentiates sensory inputs and attenuates medial prefrontal cortex inputs to the BLA. Conditions in which DA is released in the BLA, such as during the presentation of an affective stimulus, will lead to a potentiation of the strongest sensory input and a dampening of cortical inhibition over the BLA, thus augmenting the response to affective sensory stimuli.

Fig. 1.

Neuronal firing rate distribution supports the presence of two populations of BLA neurons. A, Firing rate distribution of neurons recorded in the BLA. There is a bimodal distribution that may be separated into two normal populations (p < 0.05; n = 179 neurons) with 0.5 Hz as a cutoff. Representative firing rate histograms of two spontaneously firing neurons, a fast-firing (B) and a slow-firing (C) neuron.

Fig. 2.

Parcellation of fast- and slow-firing neurons of the BLA by spike duration. A, Example trace of a fast-spiking neuron that displays a short spike duration (1.2 msec).B, Example trace of a slow-firing neuron that displays a long spike duration (4.0 msec). C, A plot of spike duration by firing rate for a sample of 90 BLA neurons demonstrates that fast-firing neurons (>0.5 Hz) tend to display short spike durations, whereas slow-firing neurons (<0.5 Hz) tend to display longer duration spikes (p < 0.01).

Fig. 3.

Antidromically activated, slow-firing BLA neurons display an increase in firing rate after DA receptor blockade.A, An example trace of a BLA neuron that follows high-frequency (300 Hz) electrical stimulation of the NAc.Arrows pointing up indicate stimulation, and arrows pointing down indicate spikes, respectively. B, Traces of antidromically evoked spikes in a slow-firing neuron in response to single NAc stimulation. The spikes display constant response latency (1) and collision (2) with a spontaneously occurring spike (3). Arrow indicates stimulus artifact. C, BLA neurons that could be antidromically activated from NAc stimulation display an increase in firing rate after systemic administration of the DA antagonist haloperidol (n = 7; *p < 0.05; Wilcoxon; circles represent neuronal firing rates prehaloperidol and posthaloperidol administration).

Fig. 4.

Opposite effects of DA receptor activation on fast-firing and slow-firing BLA neurons. A, Firing rate histogram of a fast-firing neuron that displays an increase in firing rate after systemic administration of the DA agonist apomorphine (0.09 mg/kg, i.v.) that is reversed after systemic administration of the DA antagonist haloperidol (0.30 mg/kg, i.v.). B, Firing rate histogram of a slow-firing neuron that displays a decrease in firing rate after systemic administration of apomorphine (0.12 mg/kg, i.v.) that is reversed after systemic administration of the DA antagonist raclopride (0.25 mg/kg, i.v.). Arrowsindicate the time of drug administration. C, DA agonist administration has opposite effects on fast-firing (n = 10 of 11 neurons) and slow-firing (n = 7 of 9 neurons) neurons of the BLA (*p < 0.05; error bars indicate mean ± SEM; see Results for dose ranges).

Fig. 5.

Opposite effects of DA receptor blockade on fast-firing and slow-firing BLA neurons. A, Firing rate histogram of a fast-firing neuron that displays a decrease in firing rate after systemic administration of the DA antagonist haloperidol (0.32 mg/kg, i.v.). B, Firing rate histogram of a slow-firing neuron that displays an increase in firing rate after systemic administration of haloperidol (0.31 mg/kg, i.v.).Arrows indicate time of drug administration.C, Opposite effects of systemic administration of DA antagonists on fast-firing (5 of 6 neurons) and slow-firing (8 of 9 neurons) neurons of the BLA (*p < 0.05; error bars indicate mean ± SEM; see Results for dose ranges).

Fig. 6.

Electrical stimulation of the SN/VTA exerts opposite effects on fast-firing and slow-firing neurons.A1, Averaged composites of neuronal responses to SN/VTA stimulations (stimulus time histograms for several neurons were added together and divided by the number of stimulus presentations). SN/VTA stimulation increases the firing rate of fast-firing neurons of the BLA (n = 5; p < 0.05), decreases the firing rate of slow-firing neurons (n = 4; p< 0.05) (2), and attenuates the glutamate-evoked excitation of neurons that did not display spontaneous spike discharge (n = 4; p < 0.05) (3). Arrows indicate onset of electrical stimulation (1–2 sec; 10–20 Hz; 0.5–0.6 mA).B, Example firing rate histogram of the response of a fast-firing neuron to SN/VTA stimulation before (1) and after (2) systemic administration of the DA antagonist haloperidol (0.67 mg/kg, i.v.).Vertical line indicates beginning of 1 sec SN/VTA stimulation at 10 Hz, 0.2 msec durations, 0.6 mA.

Fig. 7.

Microiontophoretic application of DA attenuates BLA neuronal firing induced by co-microiontophoresis of glutamate.A, Firing rate histogram showing that DA attenuates the neuronal firing induced by iontophoretically applied pulses of glutamate (−20 nA) in a current-dependent manner. B,Firing rate histogram showing that DA attenuates the neuronal firing induced by continuous iontophoretic application of glutamate (−20 nA) in an antidromically activated neuron. C, Plot of the current dependency of the attenuation of neuronal firing by iontophoretic application of DA (n = 20 neurons).

Fig. 8.

DA receptor activation attenuates mPFC- and MD-evoked short-latency responses in BLA neurons. A, An example trace of an MD-evoked short-latency response in a BLA neuron that did not fire spontaneously. Arrow indicates electrical stimulation artifact. B, Repre- sentative PSTHs of the attenuation of MD-evoked responses in a nonspontaneously firing BLA neuron by systemic administration of apomorphine (0.10 mg/kg) and its reversal by systemic administration of haloperidol (0.30 mg/kg). C, MD-evoked short-latency responses are attenuated after systemic administration of DA agonists (6 of 7 neurons; *p < 0.05; error bars indicate mean ± SEM). D, mPFC-evoked short-latency responses are attenuated after systemic administration of DA agonists (5 of 5 neurons; *p < 0.05; error bars indicate mean ± SEM, see Results for dose ranges).

Fig. 9.

DA agonist administration has opposite effects on MD-evoked and spontaneous firing recorded from the same neuron.A, PSTH indicating the presence of a short-latency evoked response (arrow) in a spontaneously firing neuron (top). The short-latency evoked response is attenuated, yet the spontaneous firing rate (arrowheads, the prestimulus firing rate) is increased (p < 0.05; bottom) after systemic administration of the DA agonist apomorphine (0.10 mg/kg). B, Graphic representation of the opposite changes in firing rate and MD-evoked short-latency responses recorded in the same neuron displayed inA. Additionally, systemic administration of haloperidol (0.65 mg/kg) reversed the effects of apomorphine and caused a further suppression of neuronal firing rates and potentiation of evoked spike probability to levels that surpassed predrug baseline.

Fig. 10.

DA receptor activation potentiates Te3-evoked short-latency responses in BLA neurons. A,Representative PSTHs from a nonspontaneously firing BLA neuron that displays potentiation of the Te3-evoked short-latency response after systemic administration of apomorphine (0.37 mg/kg). This effect is reversed after systemic administration of haloperidol (0.49 mg/kg).B, Systemic administration of apomorphine potentiates Te3-evoked short-latency responses in BLA neurons (9 of 10 neurons; *p < 0.05; t test; error bars indicate mean ± SEM; see Results for dose ranges).

Fig. 11.

DA receptor activation attenuates MD- and mPFC-evoked population field potentials recorded in the BLA. Traces of mPFC-evoked (A) and MD-evoked population field potentials before (black) and after (gray) systemic administration of apomorphine (mPFC, 0.88 mg/kg; MD, 0.58 mg/kg). Each trace represents 30 averaged recorded field potentials. Arrow (Stim) marks stimulus artifact.