What is the bed nucleus of the stria terminalis?

What exactly is this bed nucleus of the stria terminalis? This is a question that I, and possibly all of my colleague neuroscientists with interest in this region of the brain, get on a regular basis. Unfortunately, the simplest questions are often the most difficult to answer.

Firstly, what’s in a name? Researchers have failed to reach consensus on whether “BST” or “BNST” is the most effective acronym for their structure of interest. It seems there is little hope for clarification, as there is no scientific or grammatical justification using which we might choose one or the other. To our chagrin, both will probably continue to be commonly used. A description of the BST [sic] should start by reporting that it is a cluster of about 12 nuclei surrounding the caudal part of the anterior commissure, deep in the cerebral hemispheres. The exact number of BST nuclei varies depending on the criteria used, which are, at the moment, mostly anatomical. This may change in the future with more precise and localized permanent or reversible lesion approaches.

The BST is so named because it is located at one extremity of the stria terminalis, a bundle of axons that connects it with the amygdaloid nuclei. Although work is still needed to fully understand the function (s) of the BST, extensive anatomical studies of its connectivity suggest that it is a relay center within neurocircuits coordinating the activity of autonomic, neuroendocrine, and somatic motor systems into fully organized physiological functions and behaviours (Dong et al., 2001a,b; Dong and Swanson, 2003, 2004a, b, 2006a, b, c; Hasue and Shammah-Lagnado, 2002; Li and Kirouac, 2008; McDonald et al.,1999; Prewitt and Herman, 1998; Rodaros et al., 2007; Saggu and Lundy, 2007; Shin et al., 2008; Wood and Swann, 2005). Altogether, the BST seems to be a coordinating and relay center where descending cortical information meets ascending interoceptive and exteroceptive information regarding homeostatic states or potential changes in homeostasis. Information likely flows into the BST from exteroceptive (main and accessory olfactory, touch and nociception, gustatory) or interoceptive (energy and fluid levels, tissue damage, sexual hormone levels) sources through all central nervous system levels (from cortical to brain stem and spinal cord). The BST then has widespread descending projections to motor regions of the hindbrain that may trigger or contribute to the elaboration of coordinated physiological and behavioural responses necessary for a well-balanced homeostasis.

The BST can be roughly divided into anterior and posterior subdivisions, each containing several nuclei, which can be identified based on their projection pattern and neurochemical identity (Cassell et al., 1986; Day et al., 1999; Ju and Swanson, 1989; Ju et al., 1989; Larriva-Sahd, 2004, 2006; McDonald,1983; Moga et al.,1989; Veinante and Freund-Mercier, 1997). The anterior group (BSTant) seems to specialize in energy balance whereas the posterior group (BSTpost) may contribute more to reproduction and defense. However, the anterior and posterior BST are highly interconnected, ruling out unrelated or distinct functions for the two general areas.

Although the BST is a relatively neglected structure of the brain with respect to physiological and behavioural studies, the available data somewhat confirms the predictions made from the anatomy. To date, lesions (reversible or irreversible) or pharmacological manipulations of the BST suggest roles in the physiology of fear, food intake, social behaviours, pain, and goal-directed behaviours and the associated pathophysiological states such as anxiety, anorexia, and addiction (Ciccocioppo et al., 2003; Colussi-Mas et al., 2005; Crown et al., 2000; Delfs et al., 2000; Deyama et al., 2007, 2008, 2009; Dumont et al., 2005; Dunn and Williams, 1995; Epping-Jordan et al., 1998; Erb and Stewart,1999; Fendt et al., 2003; Gewirtz et al.,1998; Jasnow et al., 2004; Lee and Davis, 1997; Leri et al., 2002; Liu et al., 2009; Nakagawa et al., 2005; Sajdyk et al., 2008; Sullivan et al., 2004; Walker and Davis, 1997; Walker et al., 2000; Wang et al., 2001).

In the present special issue of Progress in Neuro-Psychopharmacology and Biological Psychiatry, seven groups of scientists generously contributed their time in reviewing their work and sharing their thoughts on their work on the BST, in addition to providing new and exciting data. In the first article, Walker et al. provide solid evidence that the BST manages stimuli associated with potential and non-imminent threats in contrast (or rather in complement) with the amygdaloid nuclei, which are critical for pairing unconditional stimuli with immediate threats. Along this line, Hammack et al. demonstrate both the complexity of serotoninergic modulation of BST neurons activity and how it changes in the face of stress and anxiety. Amir and Stewart next review their work on the regulation of the clock gene PER2 in the BST and the central amygdala, and discuss the key role of the BST – in particular the oval region – in circadian rhythms. Interestingly, they suggest that regulation of PER2 in the BST influences motivated behaviours in rodents. McElligot et al. gathered their work on excitatory transmission and plasticity of glutamate BST synapses with a special focus on the effects of drugs of abuse or stress on these synapses. On the other side of the engram, Sanna et al. discuss their recently reported studies of the intrinsic plasticity of BST neurons in animals chronically treated with drugs of abuse. Furthermore, Jalabert et al. review results from their respective work showing that the BST provides a major regulatory input to midbrain dopamine neurons, consistent with the role of the BST in goal-directed behaviours and the pathophysiology of addiction. Finally, Poulin et al. provide an important new set of neurochemical data that characterizes the endogenous opioid system of the BST, its specific distribution, and co-localization with immunohistochemical markers for the classic neurotransmitters GABA and glutamate.

We hope this special issue of Progress in Neuro-Psychopharmacology and Biological Psychiatry will trigger interest and excitement in this complex and intriguing region of the forebrain, and will prompt the reader to discover or revisit anatomical and physiological studies of the BST.