Forebrain mechanisms in the relief of fear: The role of the lateral septum

Abstract

The septa! region is a centrallink in a major forebrain inhibitory system. This paper presents evidence suggesting that an important function of septal inhibition is the suppression of aversive emotional states. Support for such a proposition is derived from a confluence ofthree kinds of evidence: (1) evidence that electrical stimulation ofthe septal region has the ability to inhibit aversive states; (2) evidence that lesions of the septal region reduce or abolish the ability of environmental stimuli to inhibit aversion; (3) and evidence that activity of cells in the lateral septum is increased in the presence of stimuli which inhibit aversion. It is concluded that the dynamic activity of the septal region and related areas is essential for the control and guidance of aversively motivated behavior.

Activation of corticotropin-releasing factor receptor 2 in lateral septum negatively regulates maternal defense.

“…Thus, when a female becomes a mother, behavioral neuroendocrine changes likely occur that allow a female’s first reaction to a potentially threatening stimulus, such as an intruder male, to change from flight to an active stress-coping strategy such as maternal defense. One mechanism for this behavioral switch could involve an alteration of signaling molecules, such as CRF-related peptides in LS, a region that gates reactivity to stressors (Sheehan et al, 2004) and active coping strategies (Thomas & Evans, 1983; Thomas, 1988; Yadin & Thomas, 1996; Ebner, Wotjak, Holsboer, Landgraf, & Engelmann, 1999). In addition, LS inhibition has been suggested to change how an animal perceives the relative safety of a normally fear-evoking stimulus (Yadin & Thomas, 1998); in the case of maternal defense, this may involve how a female interprets an intruder male.…”

Lesions of the perirhinal cortex interfere with conditioned excitation but not with conditioned inhibition of fear.

“…However, a few brain areas are noteworthy (see Falls & Davis, 1995a). Work by Yadin and Thomas has consistently implicated the lateral septal nucleus in the reduction of fear-related behavior (Thomas, 1988; Yadin & Thomas, 1981, 1992). There have also been suggestions that the inhibition of fear may involve primary sensory cortex (LeDoux, Romanski, & Xagoraris, 1989; Teich et al, 1989) and infralimbic–cingulate cortex (Holson, 1986; Jaskiw & Weinberger, 1992; Morgan & LeDoux, 1995; Morgan, Romanski, & LeDoux, 1993).…”

Role of cholinergic systems in pain modulation: I. Impact of scopolamine on environmentally induced hypoalgesia and pain reactivity.

“…First, all three are attenuated by administration of naltrexone, pentobarbital, and scopolamine (Grau, 1987b;Grau et al, 1981;Hyson et al, 1982;Lewis et al, 1980Lewis et al, , 1983Maier, 1989;Maier et al, 1980Maier et al, , 1983Terman et al, 1984Terman et al, , 1985 and Experiments 1 and 2 of the present study). Second, all three are blocked by both spinal transection and forebrain lesions (Grau & Meagher, 1987;Kelsey & Baker, 1983;Klein, Lovaas, Terman, & Liebeskind, 1983;Meagher &Grau, 1987, 1988Meagher etal., 1989Meagher etal., , 1990. This latter finding is of particular interest because it suggests that all three depend on neural systems in the forebrain, a point that distinguishes these examples of hypoalgesia from most other examples of shock-induced hypoalgesia (cf.…”