Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next

Abstract

Our 1992 paper, ‘The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications’, reviewed a series of (then) new and preliminary findings from cross-species studies of prepulse inhibition of the startle reflex, and commented on their implications. At the time that the report was composed, PubMed listed about 40 citations for studies using the search term ‘prepulse inhibition’. In the ensuing 25 years, the field has added about 2700 such reports, reflecting the substantial growth in interest in prepulse inhibition and its utility across a number of different experimental applications. The 30th anniversary of the Journal of Psychopharmacology provides an opportunity to comment briefly on what was described in that 1992 report, how the field has progressed in the subsequent decades, and the paths forward for studies of prepulse inhibition and its use as an operational measure of sensorimotor gating. Among these future paths, we highlight the use of prepulse inhibition as: an endophenotype for genomic studies, and a biomarker for healthy brain circuitry, which may predict sensitivity to psychotherapeutics. Our 1992 report was highly speculative and based on paper-thin empirical data, yet viewed in a certain light, it appears to have contained a basic roadmap for a journey spanning the next 25 years of prepulse inhibition research… and ‘what a long, strange trip it’s been’.

Genome wide association analysis in a mouse advanced intercross line

“…In the 240 present study, we used 1,063 male and female mice from LG x SM G50-56 to identify 126 loci for a 241 variety of traits selected for their relevance to human psychiatric and metabolic diseases (Lawson and 242 Cheverud 2010;Swerdlow et al 2016;de Wit and Phillips 2012) (Fig.3; Supplemental Table S1; 243 Supplemental Fig.S2). Whereas our previous work established AILs as an effective tool for fine-244 mapping loci identified in F2 crosses (Gonzales and Palmer 2014;Carroll et al 2017;Parker et al 2014;245 Cheng et al 2010;Samocha et al 2010;Lionikas et al 2010), this study 246 demonstrates that AILs are also a powerful fine mapping population in their own right.…”

The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the Cholinergic System in This Phenomenon

“…It is a well-known model that was developed in the second half of 20th century for neurobiology, especially psychiatry [9]. The PPI is decrease of the amplitude of the reaction to an intense sudden stimulus under conditions when a signal of lower intensity precedes it with a small interval (<500 ms).…”

“…PPI characterises the mechanisms sensorimotor information filtration (gating), which depends on the functional state of several brain structures and the activity of many neurotransmitter systems [10]. A reduced PPI is a biomarker of predisposition to schizophrenia and other psychiatric disorders [9][10][11][12][13]. At the same time, low levels of PPI are observed in healthy individuals, and the biological benefits of high levels of PPI are unclear [11].…”

“…The preconditioning (as well as postconditioning) α7 nAChRs effects are closely related to neuronal adaptive and neuroimmune antiinflammatory mechanisms in which α7 nAChRs are particularly important in protecting against hypoxic damage in peripheral organs [22][23][24][25] and the central nervous system [19,20,22,[26][27][28]. Functional α7 nAChRs have been detected in neurons [9,[29][30][31][32][33] and in cytokine-producing cells of the immune system in both the brain [20,27,29] and other organs [22, 24-26, 34, 35]. In addition, α7 nAChRs of the hippocampus and cortex also play important roles in cognitive function in norm and pathology [29,30,[36][37][38][39], and there is evidence of a relationship between PPI and cognitive disturbances in patients with schizophrenia [9,10,40].…”

“…Functional α7 nAChRs have been detected in neurons [9,[29][30][31][32][33] and in cytokine-producing cells of the immune system in both the brain [20,27,29] and other organs [22, 24-26, 34, 35]. In addition, α7 nAChRs of the hippocampus and cortex also play important roles in cognitive function in norm and pathology [29,30,[36][37][38][39], and there is evidence of a relationship between PPI and cognitive disturbances in patients with schizophrenia [9,10,40]. There are also single direct data that α7 nAChRs selectively mediate the stimulating effect of nicotine and other selective agonists on PPI [41,42].…”