Figure 5.

A summary of the physiological and behavioral functions associated with human and monkey area 25 and rodent infralimbic (IL). These representative studies illustrate, (i) the similarities and differences in the functional effects of manipulations of area 25 in monkeys and IL in rodents; (ii) how these map onto effects in humans; and (iii) where there are gaps in our knowledge. Blue bars denote reductions in activity, red bars denote increases in activity whilst green bars denote either that the direction of effects in area 25 are unclear, or that the effects may not be specific to area 25. Thus, if red and blue bars are going in the same direction (as in rodent despair), or if the same colored bars are going in opposite directions (as in rodent anxiety), the results are inconsistent. Headings above the bars indicate physiological measure if in italics, and the behavioral paradigm if non-italic. Hatching indicates correlations rather than manipulations. In terms of physiology, there is reasonable correspondence between monkey and rodent with respect to the reductions/increases in cardiovascular activity following reductions/increases in area 25/IL activity, especially during stress; although there are exceptions (see [39]). Any correspondence with the effects of stimulation in humans is unclear, however, because the excitatory versus inhibitory effects of stimulation on area 25 activity are unknown; if indeed the effects are due to changes in area 25 at all, since effects on fibers of passage cannot be ruled out. In relation to cortisol, there is agreement between correlatory findings in humans and monkeys that indicate positive correlations between cortisol levels and area 25 activity in monkeys and area 25 functional connectivity in humans. However, this similarity does not extend to rodents [57], as radiofrequency ablation of the IL increases corticosteroids; although whether the ablation effects are specific to the IL cannot be determined. Whilst immune function is related to area 25 activity in humans, this hasn’t yet been addressed in monkeys or rodents. With respect to behavior, changes in activity in area 25 in relation to depression can be variable, but successful treatment, especially in treatment resistant patients following DBS, is very often associated with reductions in area 25 activity. In line with this, the most consistent effects in both monkey area 25 and rodent IL are the overactivation-induced anhedonia-like effects. In contrast, the effects in monkeys and rodents of area 25/IL manipulations on conditioned threat responses and their extinction appear opposite, while in rodent studies the effects on despair-like and anxiety-like behaviors are inconsistent. Abl, ablation manipulation; AP5, AP-5 (NMDA antagonist); ACTH, adrenocorticotrophic hormone; Ant, Anticipatory arousal; Bic, Bicuculline (GABA_A antagonist); CoCl, Cobalt chloride (silences activity); CoT, conditioned threat; Cort, Corticosterone; CVI, Cardiac vagal index of heart rate variability; CVS, Cardiovascular system; DBS, Deep brain stimulation; dCS, d-Cycloserine (NMDA co-agonist); DHK, Dihydrokainic acid (EAAT2 inhibitor); DM, Decision making (approach-avoidance); EPM, Elevated plus maze; Ext, Extinction; ExR, Extinction recall; Fdg, Feeding behaviour; FST, Forced Swim Test; Gen, genetic manipulation; HInt, Human intruder test; HR, Heart rate; HRV, heart rate variability; IL1β, Interleukin 1β; Les, lesion manipulation; LY/C, LY341495 (mGluR2/3 antagonist) and CGP52432 (GABA_B antagonist); M, Muscimol (GABA_A agonist); MAP, mean arterial pressure; MB, Muscimol (GABA_A agonist) and baclofen (GABA_B agonist); Md, Mood; Mot, Motivational arousal; NAff, Negative affect; NSF, Novelty suppressed feeding, OF, Open Field test; Opto, Optogenetic manipulation; PAff, Positive affect; ReExt, Re-extinction; Sad, Response to sad faces; SPT, Sucrose preference test; SSRI, Selective serotonin reuptake inhibitor; Stim, Stimulation manipulation; TST, Tail suspension test; V, Veratrine (Sodium channel activator). Numbers indicate the relevant reference.