Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice

Abstract

Gap pre-pulse inhibition of the acoustic startle (GPIAS) is a behavioral paradigm used for inferring the presence of tinnitus in animal models as well as humans. In contrast to pre-pulse inhibition (PPI), the neural circuitry controlling GPIAS is poorly understood. To increase our knowledge on GPIAS, a comparative study with PPI was performed in mice combining these behavioral tests and c-Fos activity mapping in brain areas involved in the inhibition of the acoustic startle reflex (ASR). Both pre-pulses and gaps efficiently inhibited the ASR and abolished the induction of c-Fos in the pontine reticular nucleus. Differential c-Fos activation was found between PPI and GPIAS in the forebrain whereby PPI activated the lateral globus pallidus and GPIAS activated the primary auditory cortex. Thus, different neural maps are regulating the inhibition of the startle response by pre-pulses or gaps. To further investigate this differential response to PPI and GPIAS, we pharmacologically disrupted PPI and GPIAS with D-amphetamine or Dizocilpine (MK-801) to target dopamine efflux and to block NMDA receptors, respectively. Both D-amp and MK-801 efficiently decreased PPI and GPIAS. We administered Baclofen, an agonist GABAB receptor, but failed to detect any robust rescue of the effects of D-amp and MK-801 suggesting that PPI and GPIAS are GABAB-independent. These novel findings demonstrate that the inhibition of the ASR by pre-pulses or gaps is orchestrated by different neural pathways.

A role of oligodendrocytes in information processing independent of conduction velocity

“…gap perception). Consistent with previous reports from wild type mice 62,65,67,68 , shorter gaps elicited less inhibition than longer gaps (Figure 6B). Importantly, dysmyelinated Mbp neo/neo mice showed a significant decrease in the inhibition of the ASR, when triggered by different gap lengths.…”

“…First, we tested ‘gap-dependent pre-pulse inhibition of the acoustic startle reflex’ (GDIASR). This paradigm is widely used to behaviorally assess the detection of gaps within sound stimuli 62–65 . For this test we could only use hypomyelinated Mbp neo/neo mice that have no motor defects.…”

Efficacy of stimulus intensity increases and decreases as inhibitors of the acoustic startle response

“…This could indicate that the neural units responding to the onset of the intensity shift are more sensitive than the offset pathway responding to intensity decrease. The findings of Moreno‐Paublete et al () may explain why traditional prepulses (involving an increase of sound energy) and partial gaps (involving a decrease in sound energy) are both able to inhibit the startle center, and why they do so to differing degrees. Because increases and decreases in stimulus intensity activate separate neural pathways, both of which result in inhibition of the startle center, the amount of inhibition is determined by the number of cells recruited in either pathway, as well as which pathway is activated.…”

“…Changes in the sound environment preceding or coincident with a startle stimulus can modulate startle responding; continuous background noise facilitates responding (Blumenthal, Noto, Fox, & Franklin, 2006;Hoffman & Wible, 1969), whereas either a stimulus (prepulse) with onset shortly before the startle stimulus, or a gap in that background (cessation of the noise), inhibit startle (Blumenthal, 2015;Graham, 1975;Stitt, Hoffman, Marsh, & Boskoff, 1974). Moreno-Paublete, Canlon, and Cederroth (2017) found that gaps in background sound and traditional auditory prepulses activate partially separate neural pathways, yet both ultimately lead to inhibition of the caudal pontine reticular nucleus, the startle center (Fendt, Li, & Yeomans, 2001). If this is the case, complete silence (a gap) should not be required to activate the offset pathway; a moment of lower intensity background (a partial gap) might be sufficient to inhibit startle.…”

Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity

“…To this end, 104 we placed a second air puffer at the caudal side of the whisker field and a third air puffer at 105 the front of the contralateral whisker field. A startle response would be expected to be more 106 stereotypic, involving less direction-specificity and it should be suppressed by a brief pre-107 pulse (Gogan, 1970;Swerdlow et al, 1992;Moreno-Paublete et al, 2017). During a single 108 recording session, air puffs from the three different orientations were given and intermingled 109 with trials including a brief pre-pulse, all in a random order (Figure 2A).…”