P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxylase-65 and originate from cells in deep medial dorsal horn

Hughes, David I.; Mackie, Margaret; Gg, Nagy; Js, Riddell; Dj, Maxwell; Szabó, Gábor; Erdélyi, Ferenc; Veress, György; Szûcs, Péter; Antal, Miklós; Aj, Todd

doi:10.1073/pnas.0503646102

Cited by 88 publications

(128 citation statements)

References 24 publications

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“…In addition, occasional neurons of similar morphology were also observed in lamina IV. These neurons are located in the same region as group I nonreciprocal inhibitory interneurons in the cat Brink et al, 1983;Walmsley, 1991) as well as neurons identified in the mouse that are responsible for presynaptic inhibition of group Ia afferent transmission to motoneurons (i.e., supply P-boutons) (Hughes et al, 2005;Betley et al, 2009). In addition to studying morphological features, we therefore studied whether these GFPϩ neurons have properties similar to either of those populations.…”

Section: Distribution Of Gabaergic Interneurons In Gad65::gfp Micementioning

confidence: 99%

“…However, the group II inhibitory interneurons that project to motoneurons are in intermediate to ventral laminae, are primarily glycinergic, and do not project to Clarke's column. In the region where GFPϩ neurons are located in these GAD65::GFP mice, medial laminae V/VI, there have been two prominent populations of inhibitory neurons previously identified: (1) those responsible for presynaptic inhibition of group Ia afferent synapses on motoneurons (Hughes et al, 2005) and (2) those responsible for nonreciprocal inhibition (Czarkowska et al, 1981;Jankowska et al, 1981;Brink et al, 1983).…”

Section: Inhibitory Interneurons In Medial Laminae V/vimentioning

confidence: 99%

“…These GABAergic axon terminals (termed P-boutons) form axoaxonic synapses on Ia afferent fiber axon boutons, the terminals of which are identifiable with immunohistochemistry against VGLUT1 (Hughes et al, 2005). P-bouton terminals are GAD65 positive, and the GABAergic spinal neurons from which they originate have been identified and are also located in laminae V/VI (Hughes et al, 2005;Betley et al, 2009). To determine whether the GFP-positive neurons in our GAD65::GFP strain are also a source of P-boutons, we looked for immunohistochemical colabeling of GFP and GAD65 on primary afferents identified with VGLUT1.…”

Section: Axonal Projections Of Lamina V/vi Gabaergic Interneuronsmentioning

confidence: 99%

“…Mice in which the expression of green fluorescent protein (GFP) is driven by one of the glutamic acid decarboxylase (GAD65 or GAD67) isozymes responsible for synthesis of GABA has led to the identification of interneurons involved either in pain pathways (Hantman et al, 2004;Dougherty et al, 2009) or in presyn-aptic inhibition of Ia afferents (Hughes et al, 2005;Betley et al, 2009). However, there is no evidence that GFPϩ neurons in these animals postsynaptically inhibit motoneurons.…”

Section: Introductionmentioning

confidence: 99%

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Genetically Defined Inhibitory Neurons in the Mouse Spinal Cord Dorsal Horn: A Possible Source of Rhythmic Inhibition of Motoneurons during Fictive Locomotion

Wilson¹,

Blagovechtchenski²,

Brownstone³

2010

J. Neurosci.

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To ensure alternation of flexor and extensor muscles during locomotion, the spinal locomotor network provides rhythmic inhibition to motoneurons. The source of this inhibition in mammals is incompletely defined. We have identified a population of GABAergic interneurons located in medial laminae V/VI that express green fluorescent protein (GFP) in glutamic acid decarboxylase-65::GFP transgenic mice. Immunohistochemical studies revealed GFPϩ terminals in apposition to motoneuronal somata, neurons in Clarke's column, and in laminae V/VI where they apposed GFPϩ interneurons, thus forming putative reciprocal connections. Whole-cell patch-clamp recordings from GFPϩ interneurons in spinal cord slices revealed a range of electrophysiological profiles, including sag and postinhibitory rebound potentials. Most neurons fired tonically in response to depolarizing current injection. Calcium transients demonstrated by two-photon excitation microscopy in the hemisected spinal cord were recorded in response to low-threshold dorsal root stimulation, indicating these neurons receive primary afferent input. Following a locomotor task, the number of GFPϩ neurons expressing Fos increased, indicating that these neurons are active during locomotion. During fictive locomotion induced in the hemisected spinal cord, two-photon excitation imaging demonstrated rhythmic calcium activity in these interneurons, which correlated with the termination of ventral root bursts. We suggest that these dorsomedial GABAergic interneurons are involved in spinal locomotor networks, and may provide direct rhythmic inhibitory input to motoneurons during locomotion.

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Section: Distribution Of Gabaergic Interneurons In Gad65::gfp Micementioning

confidence: 99%

Section: Inhibitory Interneurons In Medial Laminae V/vimentioning

confidence: 99%

Section: Axonal Projections Of Lamina V/vi Gabaergic Interneuronsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetically Defined Inhibitory Neurons in the Mouse Spinal Cord Dorsal Horn: A Possible Source of Rhythmic Inhibition of Motoneurons during Fictive Locomotion

Wilson¹,

Blagovechtchenski²,

Brownstone³

2010

J. Neurosci.

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“…Correspondingly, ChAT-IR varicosities, including the C-terminals, and VGluT2-IR boutons did not show evidence of V1 origin. A population of LIX inhibitory boutons with intense GAD65-immunoreactivity corresponds with P boutons (Hughes et al, 2005), the boutons presynaptic to muscle primary afferents in axo-axonal contacts (Conradi, 1969). V1-derived EGFP-IR varicosities in LIX did not correspond with these intensely labeled GAD65-IR terminals (not shown), suggesting that V1-derived interneurons do not give rise to axons involved in this form of presynaptic inhibition.…”

mentioning

confidence: 99%

Postnatal phenotype and localization of spinal cord V1 derived interneurons

Álvarez

Jonas

Sapir

et al. 2005

J of Comparative Neurology

226

284

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Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calciumbuffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons.Keywords inhibitory interneurons; engrailed-1; motor control; GABA; glycine; calbindin; parvalbumin; calretinin; motoneurons; ventral horn; spinal cord; development; V1 During the past 50 years, classical studies in the spinal cord have uncovered a wealth of details about the organization of interneuronal networks that control motoneuron firing, segmental reflexes and generate locomotor patterns in mammals (Jankowska et al., 1992). These studies, which relied heavily on the physiological identification of synaptic inputs and (Renshaw 1946;Eccles et al., 1954). IaINs are characterized by inputs from sensory Ia muscle afferents, provide reciprocal inhibition to antagonistic motor pools (Eccles et al., 1956) and are modulated by RCs (Hultborn et al., 1971). Despite enormous progress in further identification of interneurons using these methods, much is unknown and this approach is not without limitations (Edgley, 2001;Jankowska, 2001). Thus a comprehensive classification of ventral interneurons into major subclasses has not yet emerged.Recent studies indicate that distinct cell types in the adult spinal cord are derived from genetically-discrete populations of embryonic neurons (Jessell, 2000;Briscoe and Ericson, 2001;Lee and Pfaff, 2001;Goulding et al., 2002, Sa...

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An Introduction to Pain and its Relation to Nervous System Disorders

Battaglia¹

2016

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Basic organisation of spinal pain pathways Primary afferent axons belonging to the somatosensory system can respond to a range of mechanical, thermal and chemical stimuli. Many of these afferents are activated by stimuli that damage (or threaten to damage) tissues, and these are known as nociceptors. Primary afferents that innervate the limbs and the trunk enter the spinal cord through the dorsal roots and form excitatory (glutamatergic) synapses with neurons in the dorsal horn. The dorsal horn contains a large number of neurons, the great majority of which have axons that arborise locally and remain in the spinal cord; these are known as interneurons and are involved in the local processing of sensory information. In addition, the dorsal horn contains projection cells-that is, neurons with axons that enter the white matter and travel rostrally to the brain. The axons of these cells are grouped into a number of different ascending tracts. The final neuronal component consists of descending axons, which originate from cells in the brain (particularly the brainstem) and terminate diffusely within the dorsal horn. Rexed (1952) divided the grey matter of the dorsal horn into six parallel laminae (numbered from dorsal to ventral), and this scheme is widely used, for example to describe the arborisation of primary afferents and the distribution of different populations of spinal neurons (Figure 1.1). The dorsal horn is somatotopically organised, the body being mapped in a bidimensional pattern onto the rostrocaudal and mediolateral axes. The other, dorsoventral dimension is arranged in a modality-specific pattern, as will be described later. Fifty years ago, Melzack and Wall (1965) proposed that neurons within the superficial dorsal horn could 'gate' the inputs from nociceptors and thus modify the perception of pain. This theory attracted a great deal of interest, and there have been numerous attempts to unravel the neuronal circuitry that underlies pain processing in the spinal cord. It turns out that this circuitry is highly complex, and we still have only a limited understanding of it. Nonetheless, it is clear that this region is very important for modulating pain in both normal and pathological states. The superficial dorsal horn is also likely to provide important targets

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P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxylase-65 and originate from cells in deep medial dorsal horn

Cited by 88 publications

References 24 publications

Genetically Defined Inhibitory Neurons in the Mouse Spinal Cord Dorsal Horn: A Possible Source of Rhythmic Inhibition of Motoneurons during Fictive Locomotion

Genetically Defined Inhibitory Neurons in the Mouse Spinal Cord Dorsal Horn: A Possible Source of Rhythmic Inhibition of Motoneurons during Fictive Locomotion

Postnatal phenotype and localization of spinal cord V1 derived interneurons

An Introduction to Pain and its Relation to Nervous System Disorders

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