Chapter 10 - Thalamic Organization
The diencephalon consists of the hypothalamus, subthalamus, dorsal thalamus and epithalmus. These structures basically surround the third ventricle, and comprise the lateral wall and floor of this ventricle. The hypothalamus has been discussed with the limbic system (section IXa). The subthalmus (including the subthalmic nucleus and zona incerta) has been discussed with the basal ganglia.
The Epithalmus
The epithalamus consists of the pineal gland and habenular nuclei. The pineal is an interesting area containing modified photoreceptor cells. These release melatonin in a circadian rhythm associated with the day/night cycle. Despite the fact that pinealocytes are modified photoreceptors, they do not normally respond directly to light in humans. They respond to circadian differences in sympathetic nervous system activity. This may be important in sleep-wake cycles and, in many species it is the critical trigger for hibernation and sexual maturation.
The habenular nuclei receive input from several limbic structures (including the ventral forebrain and septal nuclei) via the stria medullaris thalami. This tract can be seen on the third ventricular surface of the thalamus. The habenular nuclei project to the interpeduncular nucleus of the midbrain via the fasciculus retroflexus. This is a pathway by which limbic structures may influence brain stem (reticular formation) function.
General Organization of the Dorsal Thalamus
The remainder of this discussion will deal with the dorsal thalamus, usually just called the thalamus. Some of the functions of the thalamus have been discussed in prior sections. This section will put thalamic functions in a more integrated construct. The thalamus is the largest component of the diencephalon. It is the primary site of relay for all of the sensory pathways except olfaction on their way to the cerebral cortex. Even olfactory signals reach the thalamus via indirect connections with the cortical regions initially receiving the olfactory signal.
The thalamus is a site where sensory inputs can be modulated. It is also a site of relay for cerebellar and basal ganglia inputs to the cerebral cortex. Remember, these are feedback pathways, since the cerebellum and basal ganglia respond to outputs from the cerebral cortex (see sections VIIIa and VIIIb). Limbic pathways also make input to the dorsal thalamus.
All thalamic nuclei, with the exception of the reticular thalamic nucleus, project primarily to the cerebral cortex. Additionally, each portion of the thalamus receives a reciprocal connection from the same portions of the cerebral cortex whereby the cortex can modify thalamic functions. This may provide a mechanism for filtering thalamic inputs to the cerebral cortex.
All thalamic nuclei contain many inhibitory interneurons (GABAergic and peptidergic) that can modulate the transmission of signals through the thalamus. Additionally, many neuromodulatory neurotransmitter systems (such as serotonin and norepinephrine systems) have terminations within thalamic nuclei. Therefore, it appears that the ability to filter signals is important to thalamic function and plastic changes in this filtering function may be physiologically important. There are two basic types of inputs to the thalamus. The first of these is input that is being relayed the cortex. The second is modulatory input, which primarily arises from the cerebral cortex, as well as from the reticular thalamic nucleus and various brain stem areas. These modulatory pathways effect transmission.
Each thalamic projection neuron can exist in one of two basic physiological states "tonic mode" and "burst mode." Burst mode has also been called "oscillatory mode" since neurons in this state have an intrinsic rythmicity. In "tonic mode", the neurons respond like other neurons to depolarization and hyperpolarization. Burst mode is found when neurons are tonically hyperpolarized. When they are in this mode, a special class of calcium channels are opened, which result in rhythmic depolarization, producing a rhythmic burst of action potentials in the thalamic projection neurons.
During sleep, most thalamic neurons are in burst mode. During waking many thalamic neurons remain in burst mode. In burst mode, neurons cannot communicate specific information. However, if a novel stimulus is presented, the sudden change from burst to tonic mode may be a major factor in alerting the cortex. Additionally, this intrinsic rhythmicity probably contributes to the generation of cortical electroencephalographic rhythms.
The thalamus is divided into three regions that are anatomically defined by a "Y" shaped bundle of nerve fibers termed the internal medullary lamina (figure 32A). Broadly, there is an anterior, lateral and medial subdivision of the thalamus. Within each of these divisions there may be subnuclei with distinct connections. The anterior thalamic nucleus has a single nucleus, the anterior nucleus. This is between the arms of the rostral parts of the internal medullary lamina. The medial portion of the thalamus contains the medial dorsal nucleus (MD; also called the dorsal medial nucleus - DM) as well as smaller midline nuclei (located right beneath the wall of the third ventricle). The lateral region is subdivided into ventral and dorsal tiers each of which contain subnuclei.
The ventral tier of the lateral division contains the ventral posterior, the ventral lateral (VL) and ventral anterior (VA) nuclei. The ventral posterior is further divided into the ventral posteromedial (VPM) and ventral posterolateral nuclei (VPL). The dorsal tier contains, from caudal to rostral, the pulvinar, the lateral posterior (LP) and the lateral dorsal (LD) nuclei.
The intralaminar nuclei are found within the internal medullary lamina and include the central median and parafascicular nuclei. The reticular thalamic nucleus is a thin shell of neurons covering the entire lateral aspect of the thalamus. This is separated from the thalamus by the external medullary lamina.
The metathalamus includes nuclei that protrude from the posterior aspect of the pulvinar of the thalamus. These include the medial geniculate body (an auditory relay nucleus) and the lateral geniculate body (the principal visual relay).
Types of Thalamic Nuclei
There are three basic types of thalamic nuclei: i) relay nuclei; ii) association nuclei; and iii) nonspecific nuclei. Relay nuclei receive very well defined inputs and project this signal to functionally distinct areas of the cerebral cortex. These include the nuclei that relay primary sensations (the ventral posterolateral - VPL, ventral posteromedial - VPM, medial geniculate and lateral geniculate nuclei) and also the nuclei involved in feedback of cerebellar signals (ventral lateral - VL) and in feedback of basal gangliar output (part of the VL and the ventral anterior nucleus - VA). The association nuclei are the second type of thalamic nuclei and receive most of their input from the cerebral cortex and project back to the cerebral cortex in the association areas where they appear to regulate activity. The third type of thalamic nuclei are the nonspecific nuclei, including many of the intralaminar and midline thalamic nuclei that project quite broadly through the cerebral cortex, may be involved in general functions such as alerting.
Given the various functions of the thalamus, it is not surprising that each of the thalamic nuclei has distinct connections to the cerebral cortex (figure 32B). We will first discuss connections of specific nuclei before discussing the association and nonspecific nuclei.
Relay Thalamic Nuclei
The VPL and VPM nuclei are part of the somatosensory system. The VPL relays medial lemniscal and spinothalamic connections to the cerebral cortex. The VPM receives trigeminothalamic input and relays to the inferior portion of the postcentral gyrus.
The lateral and medial geniculate nuclei are specific nuclei that relay vision and hearing, respectively. The lateral geniculate receives retinotopic input via the optic tract from the contralateral homonomous visual world. This projects in a topographic manner to the primary visual cortex via the optic radiations. The optic radiations from the upper visual world loop through the temporal lobe white matter on the way to the visual cortex (Meyer's loop), while optic radiations from the lower visual world pass just deep to the parietal lobe.
The medial geniculate receives tonotopically organized auditory afferents from the inferior colliculus via the brachium of the inferior colliculus. This projects to the primary auditory cortex on the superior temporal gyrus (transverse gyrus of Heschel).
The VL receives input from the cerebellum, mainly from the dentate nucleus. There is a small input from the basal ganglia to the rostral part of the VL, as well. The VL projects to the primary motor area, area 4, of the precentral gyrus and also has a smaller projection to premotor areas. The VL is thus involved in motor feedback from the cerebellum and basal ganglia to the cerebral cortex.
The VA nucleus receives most of its input from the basal ganglia especially the medial globus pallidus and substantia nigra, parts reticulata. This projects to premotor cortex including the supplementary motor area of the frontal lobes and is involved in planning and initiating movements. The centromedian nucleus (one of the intralaminar nuclei) has reciprocal connections with the globus pallidus and with the premotor cortex. It appears to function as part of the basal gangliar feedback system.
Association Thalamic Nuclei
There are a substantial number of association nuclei. Remember, these nuclei receive the largest input directly from the cerebral cortex. The pulvinar is the largest of these association nuclei, occupying the posterior part of the dorsal tier of the thalamus. This receives afferent projections from the superior colliculus as well as from the association cortex. It projects to secondary visual areas and to association areas in the parietotemporal region. This contributes to visual perception and eye movements, probably relating to attention to these stimuli. The LP has very similar connections and function to the pulvinar.
The dorsomedial nucleus (DM; also known as the mediodorsal nucleus MD) is an association nucleus that has a medial and lateral subdivision. The lateral part receives projections from the superior colliculus, olfactory cortex and the ventral pallidum. It has efferent projections to the frontal eye fields and to the anterior cingulate cortex of the frontal lobes. This is involved in controlling eye movements and attending to visual stimuli but it also plays a role in emotional "tone".
The medial portion of the MD, along with the midline nuclei, receives inputs from several brain areas including the solitary nucleus, substantia nigra reticulata, amygdala and ventral pallidum. It projects to limbic areas of the cortex, including insular cortex, orbital frontal cortex and subcallosal region. These cortical areas are involved in autonomic regulation and emotions. Damage to this area can also impair memory as may happen with the amnestic syndrome due to alcoholism.
The anterior nucleus of the thalamus has connections similar to the LD nucleus. It receives input from the hippocampus via the mamillary bodies and projects to the posterior cingulate cortex. The functions are not entirely clear, although it appears to have some role in emotional learning.
Nonspecific Thalamic Nuclei
The reticular thalamic nucleus receives afferents from the brain stem reticular formation as well as from the cerebral cortex and thalamus. This makes a strongly inhibitory input to thalamic nuclei. This nucleus may be important in sleep wake cycles and maybe an important regulator of signals relaying through the thalamus.
Many of the intralaminar nuclei and midline nuclei have diffuse projections to the cortex and have been termed "nonspecific". These nuclei are probably mostly involved in arousal and alertness.