GABA in the Deep Layers of the Superior Colliculus/Mesencephalic Reticular Formation Mediates the Enhancement of Startle by the Dopamine D₁Receptor Agonist SKF 82958 in Rats

Abstract

GABA transmission in the deep layers of the superior colliculus/ deep mesencephalic reticular formation (deep SC/Me) mediates several motor responses, including those expressed after systemic administration of dopamine agonists. In the present study we examined the role of the deep SC/Me in the modulation of the acoustic startle reflex and its enhancement by the dopamine D 1 agonist SKF 82958. Rats were implanted with bilateral cannulas into the deep SC/Me or superficial layers of the SC (super SC) and 1 week later were infused with various compounds. The GABA A antagonist bicuculline (0, 5, and 10 ng) produced a doseand time-dependent enhancement of startle after infusion into the deep SC/Me, but not the super SC. Infusion of the GABA A agonist muscimol (0.1 g) into the deep SC/Me, but not the super SC, blocked the enhancement of startle by systemic SKF 82958 (1 mg/kg) but had no effect on baseline startle by itself. This effect was not produced by infusion of the D 1 antagonist SCH 23390(1 g) or the glutamate antagonist NBQX (0.1 g). Deposits of FluoroGold into the deep SC/Me, combined with immunohistochemistry for glutamic acid decarboxylase (GAD), confirmed a direct GABAergic input from the substantia nigra pars reticulata (SNr) to the deep SC/Me. These results suggest that GABA tone in the deep SC/Me modulates the expression of startle as well as the enhancement of startle by dopamine D 1 agonists. On the basis of these data and previous work, we have proposed a striatonigral-tectal-reticular neural pathway mediating the effects of dopamine D 1 agonists on startle. Key words: startle; superior colliculus; bicuculline; muscimol; SKF 82958; D 1 receptorThe acoustic startle reflex in rats is a rapid sensorimotor response elicited by a sudden and intense auditory stimulus (cf. Davis, 1984) and is mediated by a simple neural pathway in the brainstem consisting of cochlear root neurons (CRNs), neurons in the nucleus reticularis pontis caudalis (PnC), and motoneurons in the spinal cord (Lee et al., 1996). The amplitude of this short-latency response can be quantified easily and has been used extensively to study the neurocircuitry and neurochemistry involved in the modulation of reflex/motor behavior (cf. Davis, 1980). Along these lines, we have found that systemic administration of dopamine D 1 receptor agonists markedly increases the acoustic startle response (Meloni and Davis, 1999a). This effect is mediated in part by the activation of D 1 receptors in the substantia nigra pars reticulata (SNr; Meloni and Davis, 1997), a major output structure of the basal ganglia to premotor areas in the midbrain (Graybiel, 1984). Hence, we have been using D 1 agonist-induced enhancement of the acoustic startle response to study the neural mechanisms underlying dopaminergic control of motor behavior. In particular, we are interested in how SNr-dependent D 1 receptor agonist effects get transmitted to the primary acoustic startle pathway in the brainstem.In the present study we have focused on the deep layers of the superior c...

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“…The effects on baseline startle were surprising, as previous reports have shown dopamine receptor agonists to increase startle (Davis and Aghajanian, 1976;Meloni and Davis, 1999;Meloni and Davis, 2000). Decreases in baseline likely do not account for the results of Experiment 4, as the effect of apomorphine on nicotine withdrawal-potentiated startle was apparent following 50 mg/kg apomorphine, a dose that did not affect baseline startle.…”

Anatomically discrete functional effects of adenoviral clostridial light chain gene-based synaptic inhibition in the midbrain

“…We believe that under normal physiological conditions, the dSC/DpMe does not provide a tonic excitatory drive to the startle pathway because inactivation of the dSC/ DpMe by muscimol had little effect on baseline startle. 7 We hypothesize that viral-induced inflammation increases excitatory drive from the dSC/DpMe to the startle pathway. Thus, blockade of this increased excitatory drive by LC expression would inhibit the infection-dependent increase of startle as well as contextdependent facilitation.…”

“…In particular, the deep layers of the superior colliculus/ deep mesencephalic nucleus (dSC/DpMe) play a critical role in facilitation of the acoustic startle reflex induced by fear conditioning. [7][8][9] Inactivation of the dSC/DpMe blocks the facilitation of startle response by conditioned fear, known as fear-potentiated startle. Our recent study demonstrates that this effect is site and function specific.…”

Fear-Potentiated Startle in Rats Is Mediated by Neurons in the Deep Layers of the Superior Colliculus/Deep Mesencephalic Nucleus of the Rostral Midbrain through the Glutamate Non-NMDA Receptors

“…Among the motor reactivities involved in the deep SC/ DpMe are defensive reactions (Dean et al, 1988;Redgrave et al, 1996;Niemi-Junkola et al, 1997;Brandao et al, 2003), startle response modulation (Meloni and Davis, 2000), convulsions (Garcia-Rill et al, 1985;Hashizume et al, 2000;Ishimoto et al, 2000), and locomotor activity (Sinnamon and Stopford, 1987;Sinnamon, 1993;Jordan, 1998). The specificity of NBQX infused into this area on fear-potentiated startle compared with baseline startle suggests that amygdala terminals may release glutamate into the deep SC/DpMe when activated by a CS.…”