Inhibitory interneurons

Figure 1.3 Some possible basic neurotransmitter-synaptic arrangements for the excitation and inhibition of different neurons, (a) The single NT activates neuron B and inhibits neuron C by being able to activate both excitatory and inhibitory receptors or, more probably, acting on one receptor linked to both events. There is potential, however, for the NT to activate any inhibitory receptors that may be on B or excitatory receptors on C. (b) The same NT is used as in (a) but the excitatory receptors are now only on dendrites and separated from the inhibitory receptors only on the soma. There is less chance of unwanted mixed effects, (c) Neuron A releases distinct excitatory and inhibitory NTs from its two terminals each acting on specific and morphologically separated receptors. But this depends on a neuron being able to release two NTs. (d) Neuron A releases the same NT from both terminals. It directly excites B but inhibits C through activating an inhibitory interneuron (I) which releases an inhibitory NT onto specific receptors on C. This last scheme (d) is clearly more functional and is widely used...

Fortunately there is another way in which one neuron can excite and inhibit different neurons using just one NT. Neuron A could excite B and inhibit C by the introduction of an inhibitory interneuron the activation of which by A, using the same excitatory NT as at B, automatically inhibits C (Fig. 1.3(d)). This form of inhibition is quite common in the CNS and in fact much inhibition is mediated by these so-called short-axon interneurons and a neuron may inhibit itself through feedback via an axon collateral synapsing onto an adjacent inhibitory short-axon interneuron (Fig. 1.2). 

Lamina II is also known as the substantia gelatinosa (SG) and can be divided into two layers, the outer layer (IIo) and the inner layer (Ili). This layer is densely packed with small neurons and lacks myelinated axons. Neurons with cell bodies in Hi receive inputs from low-threshold mechanoreceptive primary afferents, while those in IIo respond to inputs from high-threshold and thermoreceptive afferents. The intrinsic cells which comprise the SG are predominantly stalk and islet cells. Stalk cells are found located in lamina IIo, particularly on the border of lamina I, and most of their axons have ramifications in lamina I although some also project to deeper layers. These cells are thought to predominantly relay excitatory transmission. Islet cells, on the other hand, are located in Hi and have been demonstrated to contain the inhibitory neurotransmitters, y-aminobutyric acid (GABA), glycine and enkephalins in their dendrites. Hence these cells have been proposed to be inhibitory interneurons. 

The uniqueness of the innervation of their targets by the granule cells underscores their function as gatekeeper. That is, excitatory principal neurons (e.g. CA3 pyramidal cell innervation of its targets in CA1) of mammalian forebrain typically innervate other excitatory neurons directly in great quantitative preference to inhibitory interneurons... 

Spinal disinhibition allows more nociceptive signal input. Following peripheral nerve injury there is a reduction in the GABAergic component of postsynaptic inhibitory currents caused by a degeneration of GABAergic interneurons [24] (Fig. 57-6). This loss of inhibition (disinhibition) results in an overall increase in the excitability of dorsal horn neurons. The degeneration of inhibitory interneurons is due to an excitotoxic effect of primary afferent ectopic activity on dorsal horn neurons [26]. 

Stretching of the muscle is sensed in the muscle spindle and leads to firing in muscle spindle afferent. These nerves travel via the dorsal root and synapse in the anterior horn of the spinal cord directly with the motor neurone to that muscle. They stimulate firing of the motor neurones, which causes contraction of the muscle that has just been stretched. The muscle spindle afferent also synapses with inhibitory interneurons, which inhibit the antagonistic muscles. This is called reciprocal innervation. 

Skeletal muscle stretched Spinal cord Inhibitory interneurones ... 

Melzack and Wall theorized that the transmission of a peripheral painful stimulus to the CNS occurs via a gate at spinal cord level. This gate comprises an inhibitory interneurone in the substantia gelatinosa that may be either stimulated or inhibited by different afferent inputs. A simple line diagram can be useful when explaining the mechanism to avoid confusion. 

The Ap fibres are examples of afferents that stimulate inhibitory interneurones (in the substantia gelatinosa (SG)) and, therefore, prevent nociceptive transmission to the CNS. The C fibres are examples of afferents that inhibit inhibitory interneurones and, therefore, enhance nociceptive transmission. Note that both types of fibre stimulate the second-order neurone (2°) directly but it is the intemeurone that modifies the transmission. 

It contracts in response to an impulse of its motor nerve. In executing motor programs, the brain sends impulses to the spinal cord. These converge on a-moto-neurons in the anterior horn of the spinal medulla. Efferent axons course, bundled in motor nerves, to skeletal muscles. Simple reflex contractions to sensory stimuli, conveyed via the dorsal roots to the motoneurons, occur without participation of the brain. Neural circuits that propagate afferent impulses into the spinal cord contain inhibitory interneurons. These serve to prevent a possible overexcitation of motoneurons (or excessive muscle contractions) due to the constant barrage of sensory stimuli. 

Centrally acting muscle relaxants (A) lower muscle tone by augmenting the activity of intraspinal inhibitory interneurons. They are used in the treatment of painful muscle spasms, e.g., in Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Diagram of the structures involved in the stretch reflex arc. I is an inhibitory interneuron E indicates an excitatory presynaptic terminal la is a primary intrafusal afferent fiber Ca2+ denotes activator calcium stored in the sarcoplasmic reticulum of skeletal muscle RyR channels indicates the Ca2+ release channels. 

In line with the latter observations, the rewarding effects of morphine are absent in knockout mice lacking receptors but persist when either of the other opioid receptors are ablated. In the VTA, opioids cause an inhibition of GABAergic inhibitory interneurons, which leads eventually to a disinhibition of dopamine neurons. 

DA control of anterior pituitary hormone secretion also mediated through transynaptic regulation of hypothalamic neurosecretory neurons. This occurs via axonal-somatic/ dendritic interactions in hypothalamic regions containing neurosecretory neuron perikarya and/or through axonal-axonal interactions on their terminals in the median eminence. Diencephalic DA neurons may regulate neuropeptide release directly via stimulatory Di or inhibitory D2 receptors located on hypothalamic neurosecretory neurons, or they may act indirectly through stimulatory and/or inhibitory interneurons. 

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