Medial forebrain bundle

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Medial forebrain bundle
Medial Forebrain Bundle.jpg
Anatomical diagram of medial forebrain bundle. These neural fibres connect the septal area in forebrain with medial hypothalamus.
Details
Identifiers
Latin fasciculus medialis telencephali
MeSH D008474
NeuroNames 433
NeuroLex ID birnlex_908
TA98 A14.1.08.955
TA2 5764
FMA 62064
Anatomical terms of neuroanatomy

The medial forebrain bundle (MFB), is a neural pathway containing fibers from the basal olfactory regions, the periamygdaloid region and the septal nuclei, as well as fibers from brainstem regions, including the ventral tegmental area and nigrostriatal pathway.

Contents

Anatomy

The MFB passes through the lateral hypothalamus and the basal forebrain in a rostral-caudal direction. The MFB has its main projections to these regions of Brodmann areas (BA) 8, 9, 10, 11, 11m. The superior frontal region of MFB projects to BA 8, 9, 10; the rostral middle frontal projects to dorsolateral prefrontal cortex (BA 9, 10); lateral orbitofrontal of MFB shows its projections to nucleus accumbens septi (NAC) and ventral striatum as subcortical reward associated structures. [1]

It contains both ascending and descending fibers. The mesolimbic pathway, which is a collection of dopaminergic neurons that projects from the ventral tegmental area to the nucleus accumbens, is a component pathway of the MFB. [2]

The MFB is one of the two major pathways connecting the limbic forebrain, midbrain, and hindbrain. The other one is the dorsal diencephalic conduction (DDC) system. The two pathways seem to have parallel neural circuits, and share similar physiology and function. [3]

Function

It is commonly accepted that the MFB is a part of the reward system, involved in the integration of reward and pleasure. [4] Electrical stimulation of the medial forebrain bundle is believed to cause sensations of pleasure. This hypothesis is based upon intracranial self-stimulation (ICSS) studies. Animals will work for MFB ICSS, and humans report that MFB ICSS is intensely pleasurable. [5]

Another research technique that was used in determining the function of the MFB was microdialysis. [6] Reinforcing electrical stimulation of the MFB using this method has shown to cause a release in dopamine in the nucleus accumbens. Other microdialysis studies have shown that the presence of natural reinforcers such as food, water, and a sex partner cause a release in dopamine in the nucleus accumbens. This shows that the electrical stimulation of the MFB causes a similar effect compared to natural reinforcers.

The medial forebrain bundle has been shown to be linked to an individual's grief/sadness system through regulation of the individual's seeking/pleasure system. [7]

Potential role in diagnosis/treatment

The medial forebrain bundle may serve as a target in treating treatment-resistant depression. [8] Since the MFB connects areas of the brain which are involved with motivated behavior, mood regulation, and antidepressant response the stimulation of the MFB through deep brain stimulation could be an effective form of treatment. Subjects that receive the deep brain stimulation treatment in the medial forebrain bundle have been reported to have high remission rates with normative functioning and no adverse side effects.

The medial forebrain bundle may also serve to study abuse-related drug effects through intracranial self-stimulation. [9] ICSS targets the MFB at the level of the lateral hypothalamus and elicits a range of responses from the subject through stimulation to acquire a baseline of responses. From this baseline the subject is then exposed to varying levels of stimuli in that are high/low in amplitude and frequency. These responses are then compared to the baseline of the subject to detect for sensitivity to the stimuli. Based on the sensitivity of the response from the subject, a level of inference on the drug abuse potential can be made.


Animal research

In animal studies studying the effects of Levodopa-induced dyskinesia, a major complication in the treatment of Parkinson's disease, lesions in the medial forebrain bundle show a maximum level of severity and sensitivity to levodopa and provide insight into the mechanisms of Levodopa-induced dyskinesia. [10] Other lesions in the mouse, particularly in the striatum 6-OHDA, show a variable sensitivity to levodopa and shows the difference in lesion severity based on location.

In a study with rats, using intracranial self-stimulation implanted in the medial forebrain bundle, rats treated with nicotine and methamphetamine showed an increased speed at which they pressed a lever to induce self-stimulation. [11] The study indicates that the medial forebrain bundle may be directly linked to motivational behavior that is induced by drugs.

In a research on rats, the deep brain stimulation (DBS) on the MFB causes an increase in dopamine for 40 seconds which is above baseline but after 40 seconds, it wasn't increased above baseline. [12]

Related Research Articles

Neurotransmitter Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.

Striatum Nucleus in the basal ganglia of the brain

The striatum, or corpus striatum, is a nucleus in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamatergic and dopaminergic inputs from different sources; and serves as the primary input to the rest of the basal ganglia.

Substantia nigra Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

Basal ganglia Group of subcortical nuclei involved in the motor and reward systems

The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an external and internal region, and in the division of the striatum. The basal ganglia are situated at the base of the forebrain and top of the midbrain. Basal ganglia are strongly interconnected with the cerebral cortex, thalamus, and brainstem, as well as several other brain areas. The basal ganglia are associated with a variety of functions, including control of voluntary motor movements, procedural learning, habit learning, conditional learning, eye movements, cognition, and emotion.

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.

Nucleus accumbens Region of the basal forebrain

The nucleus accumbens is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

Dopaminergic pathways Projection neurons in the brain that synthesize and release dopamine

Dopaminergic pathways in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons or dopamine neurons.

Nigrostriatal pathway

The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum in the forebrain. It is one of the four major dopamine pathways in the brain, and is critical in the production of movement as part of a system called the basal ganglia motor loop. Dopaminergic neurons of this pathway release dopamine from axon terminals that synapse onto GABAergic medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), located in the striatum.

Ventral tegmental area Group of neurons on the floor of the midbrain

The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.

Motivational salience is a cognitive process and a form of attention that motivates or propels an individual's behavior towards or away from a particular object, perceived event or outcome. Motivational salience regulates the intensity of behaviors that facilitate the attainment of a particular goal, the amount of time and energy that an individual is willing to expend to attain a particular goal, and the amount of risk that an individual is willing to accept while working to attain a particular goal.

Habenula

In neuroanatomy, habenula originally denoted the stalk of the pineal gland, but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus. The habenular nucleus is a set of well-conserved structures in all vertebrate animals.

Septal area

The septal 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, and refers to the nearby septum pellucidum.

Olfactory tubercle Area at the bottom of the forebrain

The olfactory tubercle (OT), also known as the tuberculum olfactorium, is a multi-sensory processing center that is contained within the olfactory cortex and ventral striatum and plays a role in reward cognition. The OT has also been shown to play a role in locomotor and attentional behaviors, particularly in relation to social and sensory responsiveness, and it may be necessary for behavioral flexibility. The OT is interconnected with numerous brain regions, especially the sensory, arousal, and reward centers, thus making it a potentially critical interface between processing of sensory information and the subsequent behavioral responses.

Medium spiny neuron Type of GABAergic neuron in the striatum

Medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), are a special type of GABAergic inhibitory cell representing 95% of neurons within the human striatum, a basal ganglia structure. Medium spiny neurons have two primary phenotypes : D1-type MSNs of the direct pathway and D2-type MSNs of the indirect pathway. Most striatal MSNs contain only D1-type or D2-type dopamine receptors, but a subpopulation of MSNs exhibit both phenotypes.

Brain stimulation reward (BSR) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by James Olds and Peter Milner. BSR can serve as a robust operant reinforcer. Targeted stimulation activates the reward system circuitry and establishes response habits similar to those established by natural rewards, such as food and sex. Experiments on BSR soon demonstrated that stimulation of the lateral hypothalamus, along with other regions of the brain associated with natural reward, was both rewarding as well as motivation-inducing. Electrical brain stimulation and intracranial drug injections produce robust reward sensation due to a relatively direct activation of the reward circuitry. This activation is considered to be more direct than rewards produced by natural stimuli, as those signals generally travel through the more indirect peripheral nerves. BSR has been found in all vertebrates tested, including humans, and it has provided a useful tool for understanding how natural rewards are processed by specific brain regions and circuits, as well the neurotransmission associated with the reward system.

Reward system Group of neural structures responsible for motivation and desire

The reward system is a group of neural structures responsible for incentive salience, associative learning, and positively-valenced emotions, particularly ones involving pleasure as a core component. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.

SR-142948 Chemical compound

SR-142948 is a drug used in scientific research which is a non-peptide antagonist selective for the neurotensin receptors, although not selective between subtypes.

The ventral pallidum (VP) is a structure within the basal ganglia of the brain. It is an output nucleus whose fibres project to thalamic nuclei, such as the ventral anterior nucleus, the ventral lateral nucleus, and the medial dorsal nucleus. The VP is a core component of the reward system which forms part of the limbic loop of the basal ganglia, a pathway involved in the regulation of motivational salience, behavior, and emotions. It is involved in addiction.

Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.

Meaghan Creed Canadian Neuroscientist

Meaghan Creed is a Canadian neuroscientist and assistant professor of anesthesiology at Washington University in St. Louis, Missouri. Creed has conducted research on understanding and optimizing deep brain stimulation in the basal ganglia for the treatment of neurological and psychiatric disorders. Her work has been recognized at the national and international level by Pfizer, the American Association for the Advancement of Science (AAAS), and the Rita Allen Foundation.

References

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