Brainstem Circuits Controlling Action Diversification
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- Movement oscillations
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n tr a i n m e n t Licking: IRt/PCRt Breathing: (pre)BötC/ VRG Whisking: vIRt Expiration Protraction Retraction Inspiration
Protrusion Retraction
vGlut2
+ vGAT
+ Dbx1
+ 7N 5N 12N BötC Phrenic MN Diaphragm a b Figure 3 Schematic diagram illustrating the close spatial proximity of brainstem neurons implicated in orofacial and respiratory behaviors regulated by brainstem circuits. (a) Top-down anatomical depiction of the BötC, preBötC, rVRG, IRt, and PCRt. Excitatory vGlut2 (teal) and inhibitory vGAT (purple) neurons, as well as developmentally Dbx1-originating (blue) neurons, are shown. The rostrocaudal boundary between MRF and PRF is indicated along with relevant cranial motor nuclei (gray). (b) Depiction of licking, breathing, and whisking behaviors; the implicated brainstem structures; and how rhythms between these behaviors can be synchronized. The breathing rhythm can entrain the whisking rhythm, indicating close collaboration between relevant circuit elements. Abbreviations: 5N, fifth motor nucleus; 7N, seventh motor nucleus; 12N, hypoglossal motor nucleus; BötC, Bötzinger complex; Dbx1, developing brain homeobox protein 1; IRt, intermediate reticular nucleus; MN, motor neuron; MRF, medullary reticular formation; PCRt, parvicellular reticular nucleus; preBötC, pre-Bötzinger complex; PRF, pontine reticular formation; rVRG, rostral ventral respiratory group; vGAT, vesicular GABA transporter; vGlut2, vesicular glutamate transporter 2; vIRt, vibrissa zone of the intermediate reticular nucleus. maintain a strong oscillatory component with rhythmic repetition of the same movement at a specific frequency (Kurnikova et al. 2017, McElvain et al. 2018). Work on a number of neuronal networks that produce rhythmic outputs has suggested that neurons with intrinsic oscillatory capacity contribute in important ways through their physiolog- ical properties even within very simple networks (Marder & Bucher 2001). For breathing, several brainstem regions with oscillatory properties linked to behavior were identified, most notably the rhythmic oscillators within the pre-Bötzinger complex (preBötC), the Bötzinger complex, and the parafacial respiratory groups regulating inspiration and expiration during breathing (Del Negro et al. 2018, Moore et al. 2014) (Figure 3). Several studies, summarized below, have addressed the cellular organization, subpopulation identity, and potential interactions between these circuits and those involved in the regulation of orofacial movements and breathing. Motor neurons innervating the oral and facial muscles used to produce orofacial movements are clustered into specific brainstem motor nuclei and project to their target muscles through cranial motor nerves (Guthrie 2007). One recent approach to uncovering the organizational
Annu. Rev. Neurosci. 2019.42:485-504. Downloaded from www.annualreviews.org Access provided by Koc University on 06/13/21. For personal use only.
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principles of networks underlying orofacial behaviors has been to study the organization of premotor neurons to the brainstem motor neurons responsible for driving respective behaviors. The overall, direct synaptic inputs to specific motor neurons were mapped through application of monosynaptic rabies viruses to reveal organizational differences between premotor neurons connecting to motor neuron pools innervating functionally distinct limb muscles (Stepien et al. 2010, Tripodi et al. 2011, Wickersham et al. 2007). In the context of orofacial and respiratory behaviors, studies analyzing the last-order premotor neuron distribution for different oral, facial, and phrenic motor neuron pools also revealed interesting organizational differences (Deschenes et al. 2016, Sreenivasan et al. 2015, Stanek et al. 2014, Takatoh et al. 2013, Wu et al. 2017). The preBötC, the site of oscillatory rhythmic activity coupled with the inspiratory respiration cycle, has almost no direct connections to diaphragm-innervating phrenic motor neurons (Del Negro et al. 2018, Smith et al. 1991). Instead, the preBötC signals through the rostral ventral res- piratory group (rVRG) to access phrenic motor neurons (Del Negro et al. 2018, Feldman et al. 2013). A recent study showed that both structures share the developmental expression of the tran- scription factor Dbx1 (Wu et al. 2017), demonstrating that the V0 progenitor domain does not only generate preBötC neurons (Cui et al. 2016) within the breathing network. Moreover, Dbx1 + rVRG neurons connect to phrenic motor neurons on both sides (Wu et al. 2017), ensuring tight inspirational control through regulation of the diaphragm muscle across the midline. Neurons in preBötC can also be influenced to produce different breathing behaviors according to motiva- tional and physiological need. To induce a sigh, preBötC neurons are regulated by a population of only 200 upstream neurons in the retrotrapezoid nucleus/parafacial respiratory group, and these neurons are marked by the expression of bombesin-like neuropeptides (P. Li et al. 2016). Recent work revealed that premotor neurons connected to different brainstem motor neurons can be in close proximity to each other or even intermingled. For example, neurons premotor to facial motor neurons controlling whisking movements are close to and within the preBötC (Sreenivasan et al. 2015, Takatoh et al. 2013). These premotor neurons show mixed neurotrans- mitter phenotypes constituting potentially different premotor populations responsible for the pro- traction and retraction phases of whisking, reinforcing the concept of distinct subpopulations con- trolling specific motor behaviors (Takatoh et al. 2013). The spatial proximity of vibrissa premotor neurons to the preBötC as well as the rhythmic nature of whisking itself raises the question of whether a potential oscillatory center for rhythmic whisking interacts with the circuits control- ling breathing. Breathing and whisking are functionally tightly coupled, but each can occur in the absence of the other (Moore et al. 2013), which suggests that linked but distinct neuronal circuitry is respon- sible for respective oscillatory control mechanisms. Additionally, since the breathing rhythm can reset the whisking rhythm but not vice versa, the preBötC seems to act as a master regulator of these behaviors (Kleinfeld et al. 2014, Moore et al. 2013) (Figure 3). Functionally, the intermedi- ate reticular nucleus (IRt), a subregion of the brainstem that is sometimes also referred to as the intermediate band of the reticular formation, is in close proximity to the preBötC and the site of whisker premotor neurons, and it harbors neurons whose activity is tightly locked with rhythmic whisking movements (Deschenes et al. 2016, Moore et al. 2013, Takatoh et al. 2013) (Figure 3). A combination of activation and lesion experiments provides evidence for the sufficiency and neces- sity of this region for whisking, demonstrating its role as an oscillatory center under the potential master regulation of the preBötC (Deschenes et al. 2016, Moore et al. 2013). As a further exten- sion of these findings on closely spaced and interacting brainstem networks, oscillatory activity coupled to licking movements as well as the necessity for licking has also been attributed to the IRt (Travers et al. 2000) (Figure 3). The circuits controlling chewing, a behavior that is not phase locked with breathing (McFarland & Lund 1993), also appear to reside within the rather lateral
Annu. Rev. Neurosci. 2019.42:485-504. Downloaded from www.annualreviews.org Access provided by Koc University on 06/13/21. For personal use only.
NE42CH23_Arber ARjats.cls May 29, 2019 7:37
brainstem but rostrally to the breathing and whisking oscillators (Dellow & Lund 1971, Kolta et al. 2007, Morquette & Kolta 2014). What is the circuit architecture controlling these interrelated behaviors? A common denom- inator in using anterograde, retrograde, and transsynaptic tracers is that most premotor neurons innervating orofacial and breathing motor neurons reside in intermediate to lateral brainstem areas that occupy partly intermingling or distinct regional hot spots, which are prominently lo- cated within the IRt, parvicellular reticular nucleus (PCRt), and preBötC regions (Deschenes et al. 2016, Sreenivasan et al. 2015, Stanek et al. 2014, Takatoh et al. 2013, Wu et al. 2017). Premo- tor neurons are also molecularly diverse, but common principles are beginning to emerge for some behaviors (Wu et al. 2017). It is currently unclear whether the circuits responsible for dif- ferent behaviors engage shared neuronal populations. Behavioral and electrophysiological exper- iments suggest that individual oscillatory centers control distinct movements, including swallow- ing, licking, and whisking, and that the breathing oscillator can act as a master regulator (Moore et al. 2014) (Figure 3). Taken together, brainstem circuits controlling orofacial and breathing behaviors are made up of specific neuronal subpopulations responsible for individual motor at- tributes that are tightly coupled to enable the complex behaviors present during exploration or feeding. An interesting aspect that has not been addressed yet is the potential interaction between oro- facial and breathing circuits with the networks involved in skilled forelimb movements or loco- motion. Orofacial behaviors are coordinated with body actions occurring during natural complex movements (Figure 1), for example, reaching for and consuming food, during which the mouth opens to take up food that is subsequently chewed and swallowed. To find food, animals explore the environment; hunt at high speed, requiring an increase in the respiratory rate; and fight with and kill their prey, again requiring tight coordination between the body and orofacial muscles. Now that the specific brainstem subpopulations responsible for orofacial, breathing, and body behaviors are beginning to be identified, studies that clarify the interactions and possible com- petitions between different neuronal populations and how complex behaviors are coordinated through brainstem motor circuitry at a more global level will be possible. Yüklə 1,32 Mb. Dostları ilə paylaş:
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