The septal area (medial olfactory area), consisting of the lateral septum and medial septum, is an area in the lower, posterior part of the medial surface of the

frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove b ...

, and refers to the nearby septum pellucidum. The septal nuclei are located in this area. The septal nuclei are composed of medium-size neurons which are classified into dorsal, ventral,

medial Medial may refer to: Mathematics * Medial magma, a mathematical identity in algebra Geometry * Medial axis, in geometry the set of all points having more than one closest point on an object's boundary * Medial graph, another graph that re ...

, and caudal groups. The septal nuclei receive reciprocal connections from the

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (O ...

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex v ...

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...

midbrain The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal ( alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...

, habenula,

cingulate gyrus The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the c ...

, and

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all direction ...

. The septal nuclei are essential in generating the

theta rhythm Theta waves generate the theta rhythm, a neural oscillation in the brain that underlies various aspects of cognition and behavior, including learning, memory, and spatial navigation in many animals. It can be recorded using various electrophysio ...

of the hippocampus. The septal area (medial olfactory area) has no relation to the sense of smell, but it is considered a pleasure zone in animals. The septal nuclei play a role in reward and reinforcement along with the

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hypot ...

. In the 1950s, Olds & Milner showed that rats with electrodes implanted in this area will self-stimulate repeatedly (i.e., press a bar to receive electric current that stimulate the neurons). Experiments on the septal area of humans have taken place since the 1960s.

Connections

The septal area is located on the lower posterior part of the frontal lobe. The septal area refers to the nearby septum pellucidum. It is located underneath the

corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental ...

and in front of the

lamina terminalis The median portion of the wall of the forebrain consists of a thin lamina, the lamina terminalis, which stretches from the interventricular foramen (Foramen of Monro) to the recess at the base of the optic stalk (optic nerve) and contains the va ...

. The lamina terminalis is a layer of gray matter that connects the optic chiasma and the

anterior commissure The anterior commissure (also known as the precommissure) is a white matter tract (a bundle of axons) connecting the two temporal lobes of the cerebral hemispheres across the midline, and placed in front of the columns of the fornix. In most exist ...

. The septal nuclei are in the septal area, and are essential in generating the

of the

. The dorsal septum projects to the lateral

preoptic area The preoptic area is a region of the hypothalamus. MeSH classifies it as part of the anterior hypothalamus. TA lists four nuclei in this region, (medial, median, lateral, and periventricular). Functions The preoptic area is responsible for ther ...

, lateral hypothalamus, periventricular hypothalamus and midline thalamus. Fibers from the ventral half of the septum project topographically to the hippocampal formation, thalamus, hypothalamus and midbrain. Specifically, neurons located along the midline in the vertical limb of the

diagonal band of Broca The diagonal band of Broca is one of the basal forebrain structures that are derived from the ventral telencephalon during development. This structure forms the medial margin of the anterior perforated substance. This brain region was described ...

project through the dorsal fornix to all CA fields of the dorsal hippocampus and adjacent subicular cortex. Other fibers from this region project through the stria medullaris to the medial and lateral habenular nuclei, the paratenial and anteromedial nucleus of the thalamus, and through the medial forebrain bundle to the pars posterior of the medial mammillary nucleus. Cells located in the intermediolateral septum also project through the lateral part of the fimbria to all CA fields of the ventral hippocampus and adjacent subicular and entorhinal cortices. These cells also send fibers through the stria medullaris to the lateral habenular nucleus and mediodorsal thalamic nucleus. Other axons arising from these cells descend through the medial forebrain bundle to terminate in a region dorsal to the interpeduncular nucleus. The lateral septum is a relay center for connections from the CA3 of the

to the ventral tegmental area. These connections help link reward signals with the context in which they occur. Fibers from the most lateral part of the ventral septum (i.e., bed nucleus of the anterior commissure) project through the

stria terminalis The stria terminalis (or terminal stria) is a structure in the brain consisting of a band of fibers running along the lateral margin of the ventricular surface of the thalamus. Serving as a major output pathway of the amygdala, the stria termin ...

to the ventral subiculum. In addition, cells located in the horizontal limb of the diagonal band project massively to the pars posterior of the medial mammillary nucleus, the ventral tegmental area, and amygdala.

Functions of the lateral septum

The lateral septum and movement and reward

The lateral septum is involved in a variety of functions, including emotional, motivational, and spatial behavior. It has been suggested that the LS may regulate interactions between the hippocampus and other regions that mediate goal directed behavior, such as the ventral tegmental area. Firing of LS neurons is modulated by both speed and acceleration and spatial location, and that firing is also related to reward and context. It has thus been suggested that the lateral septum may incorporate movement into the evaluation of environmental context with respect to motivation and reward.

Lateral septum and social behavior

Inhibitory GABA, and excitatory

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

, which regulate lateral septum (LS) activity, have been found to be increased during social play in juvenile rats. No sex differences were found in extracellular GABA concentrations during social playing, however, glutamate plays a major role in female social playing. When glutamate receptors are blocked in the LS pharmacologically, there is a significant decrease in female social playing, while males had no decrease in playing. This suggests that in the lateral septum, GABA neurotransmission is involved in social play behavior regulation in both sexes, while glutamate neurotransmission is sex-specific, involved in regulation of social play only in female juvenile rats.

Lateral septum and reproduction

Experiments have shown that both testosterone and

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues incl ...

, when implanted directly into the lateral septum of male rats, caused a significant rise in serum LH and FSH levels, while not significantly increasing serum testosterone and dihydrotestosterone levels respectively. This indicates that the effect is occurring through testosterone receptors and independently of conversion to estrogen via aromatization. As of now, it is unclear, what exact pathway is mediating this phenomenon. Septal lesions significantly decreased serum LH and testosterone levels in male rats, while FSH and

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...

production were unaffected by the surgery. Electrical stimulation of the septum induced the elevation of serum LH and FSH levels. These data suggest that the lateral and/or the medial septum may play a role in the control of GnRH/

gonadotropin Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/ chori ...

secretion, and thus, the reproductive axis.

Lateral septum and memory

Despite the diverse direct projection system between the hippocampus and the lateral septum, the first pieces of evidence regarding the role of latter brain area in memory formation and retention have only started to emerge as of 2022. However, recent research has started to shed light on the potentially diverse roles of the lateral septum.

Social memory

The roles of the lateral septum in formation of social memories remain unclear and controversial. It is clear, that some role is being played, as

oxytocin Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytoci ...

and

vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then ...

, when administered into the lateral septum after social training were able to enhance memory formation, while their respective receptor blockers had the opposite effect. However, data on effects of pre-training administration of these compounds is mixed, hence the lack of consensus.

Fear memory

Pieces of evidence suggesting the role the lateral septum could be playing in fear memory formation and consolidation have started emerging at the end of the XX. century. Inhibitory avoidance tasks using footshock chambers on mice were deployed to study the effects of the disruption of the lateral septum and hippocampal inputs on fear memory formation and retrieval respectively. In both cases, fear memory formation/retrieval was impaired, supporting the hypothesis that hippocampal projections to the lateral septum are at least in part responsible for these mechanisms. The lateral septum could also prove essential in fear memory consolidation. Post-shock adminitration of CRF into the lateral septum enhanced fear memory in the relelvant context;E H Lee (1995) Chin J Physiol Corticotropin-releasing factor injected into the lateral septum improves memory function in rats 1995;38(3):200 PMID: 8697897 however, this finding still needs to be supported by further studies.

References

External links

* {{Authority control Cerebrum Limbic system