Trisynaptic circuit
The trisynaptic circuit or trisynaptic loop is a relay of synaptic transmission in the hippocampus. The circuit was initially described by the neuroanatomist Santiago Ramon y Cajal,[1] in the early twentieth century, using the Golgi staining method. After the discovery of the trisynaptic circuit, a series of research has been conducted to determine the mechanisms driving this circuit. Today, research is focused on how this loop interacts with other parts of the brain, and how it influences human physiology and behaviour. For example, it has been shown that disruptions within the trisynaptic circuit lead to behavioural changes in rodent and feline models.[2]
The trisynaptic circuit is a
EC → DG via the perforant path (synapse 1), DG → CA3 via mossy fibres (synapse 2), CA3 → CA1 via schaffer collaterals (synapse 3)[3]
Structures
Entorhinal cortex
The
Dentate gyrus
The dentate gyrus (DG) is the innermost section of the hippocampal formation. The dentate gyrus consists of three layers: molecular, granular, and polymorphic. Granule neurons, which are the most prominent type of DG cells, are mainly found in the granular layer. These granule cells are the major source of input of the hippocampal formation, receiving most of their information from layer II of the entorhinal cortex, via the perforant pathway. Information from the DG is directed to the pyramidal cells of CA3 through mossy fibres. Neurons within the DG are famous for being one of two nervous system areas capable of neurogenesis, the growth or development of nervous tissue.
Cornu ammonis 3
The
Cornu ammonis 1
The CA1 is the region within the hippocampus between the subiculum, the innermost area of the hippocampal formation, and region CA2. The CA1 is separated from the dentate gyrus by the hippocampal sulcus. Cells within the CA1 are mostly pyramidal cells, similar to those in CA3. The CA1 completes the circuit by feeding back to the deep layers, mainly layer V, of the entorhinal cortex.
Brain areas associated with the trisynaptic circuit
There are many brain structures that transmit information to, and from the trisynaptic circuit. The activity of these different structures can be directly or indirectly modulated by the activity of the trisynaptic loop.
Fornix
The fornix is a C-shaped bundle of axons that begins in the hippocampal formation of both hemispheres, referred to as the fimbria, and extend through the
Cingulate gyrus
The
Mammillary bodies
The
Thalamus
The thalamus is a bundle of nuclei located between the cerebral cortex and the midbrain. Many of the thalamic nuclei receive inputs from the hippocampal formation. The mammillothalamic tract relays information received from the mamillary bodies (via the fornix) and transmits it to the anterior nuclei of the thalamus. Research has shown that the thalamus plays a key role with respect to spatial and episodic memories.[6]
Association cortex
The association cortex includes most of the cerebral surface of the brain and is responsible for processing that goes between the arrival of input in the primary sensory cortex and the generation of behaviour. Receives and integrates information from various parts of the brain and influences many cortical and subcortical targets. Inputs to the association cortices include the primary and secondary sensory and motor cortices, the thalamus, and the brain stem. The association cortex projects to places including the hippocampus, basal ganglia, and cerebellum, and other association cortices. Examination of patients with damages to one or more of these regions, as well as noninvasive brain imaging, it has been found that the association cortex is especially important for attending to complex stimuli in the external and internal environments. The temporal association cortex identifies the nature of stimuli, while the frontal association cortex plans behavioural responses to the stimuli.[7]
Amygdala
The amygdala is an almond-shaped group of nuclei found deep and medially within the temporal lobes of the brain. Known to be the area of the brain responsible for emotional reaction, but plays an important role in processing of memory and decision making as well. It is part of the limbic system. The amygdala projects to various structures in the brain including the hypothalamus, the thalamic reticular nucleus, and more.
Medial septum
The
Relationship with other physiological systems
Role in rhythm generation
It has been proposed that the trisynaptic circuit is responsible for the generation of hippocampal
Respiratory system
Studies have shown that the respiratory system interacts with the brain in generating theta oscillations in the hippocampus. There are numerous studies on the different effects of oxygen concentration on hippocampal theta oscillations, leading to implications of anesthetic use during surgeries, and influence on sleep patterns. Some of these oxygen environments include
There are physiological and psychological disorders related to prolonged exposure to hypoxic conditions. For example, sleep apnea[12] is a condition where there is partial, or complete, blockage of breathing during sleep. In addition, the respiratory system linked to central nervous system via base of brain. Thus, prolonged exposure to low oxygen concentration has detrimental effects on the brain.
Sensorimotor system
Experimental research has shown that there are two prominent types of theta oscillation which are each associated with different related to a motor response.[13] Type I theta waves correspond with exploratory behaviours including walking, running, and rearing. Type II theta waves are associated with immobility during the initiation or the intention of initiation of a motor response.
Limbic system
Theta oscillations generated by the trisynaptic loop have been shown to be synchronized with brain activity in the anterior ventral thalamus. Hippocampal theta has also been linked to the activation of the anterior medial and the anterior dorsal areas of the thalamus.[14] The synchronization between these limbic structures and the trisynaptic loop is essential for proper emotional processing.
See also: EC-hippocampus system
References
- ^ Andersen, P. (1975). Organization of hippocampal neurons and their interconnections. In R.L. Isaacson & K.H. Pribram (Eds.) The Hippocampus Vol. I(pp. 155-175), New York, Plenum Press.
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- ^ Amaral DG, Witter, MP. 1995. Hippocampal formation. In: Paxinos G, editor. The rat nervous system, 2nd ed. San Diego: Academic Press.
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- ^ Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Chapter 26, The Association Cortices. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11109/
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- ^ What is in the composition of air n.d. Retrieved October 27, 2014 from http://chemistry.about.com/od/chemistryfaqs/f/aircomposition.htm.
- ^ WebMD. (2012, October 5). Sleep apnea. Retrieved October 4, 2014 from http://www.webmd.com/sleep-disorders/guide/understanding-obstructive-sleep-apnea-syndrome.
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