Dopamine innervation of the monkey mediodorsal thalamus: Location of projection neurons and ultrastructural characteristics of axon terminals

Neuroscience ◽  
2006 ◽  
Vol 143 (4) ◽  
pp. 1021-1030 ◽  
Author(s):  
D.S. Melchitzky ◽  
S.L. Erickson ◽  
D.A. Lewis
Keyword(s):  
Projection Neurons ◽  
Mediodorsal Thalamus ◽  
Axon Terminals ◽  
Ultrastructural Characteristics ◽  
Dopamine Innervation

scholarly journals Similarities and differences in circuit responses to applied Gly1-SIFamide and peptidergic (Gly1-SIFamide) neuron stimulation

2019 ◽  
Vol 121 (3) ◽  
pp. 950-972 ◽  
Author(s):  
Dawn M. Blitz ◽  
Andrew E. Christie ◽  
Aaron P. Cook ◽  
Patsy S. Dickinson ◽  
Michael P. Nusbaum
Keyword(s):  
Activity Patterns ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Gastric Mill ◽  
Stomatogastric Nervous System ◽  
Cancer Borealis ◽  
Axon Terminals ◽  
Motor Circuits ◽  
Commissural Neuron ◽  
Functional Context

Microcircuit modulation by peptides is well established, but the cellular/synaptic mechanisms whereby identified neurons with identified peptide transmitters modulate microcircuits remain unknown for most systems. Here, we describe the distribution of GYRKPPFNGSIFamide (Gly1-SIFamide) immunoreactivity (Gly1-SIFamide-IR) in the stomatogastric nervous system (STNS) of the crab Cancer borealis and the Gly1-SIFamide actions on the two feeding-related circuits in the stomatogastric ganglion (STG). Gly1-SIFamide-IR localized to somata in the paired commissural ganglia (CoGs), two axons in the nerves connecting each CoG with the STG, and the CoG and STG neuropil. We identified one Gly1-SIFamide-IR projection neuron innervating the STG as the previously identified modulatory commissural neuron 5 (MCN5). Brief (~10 s) MCN5 stimulation excites some pyloric circuit neurons. We now find that bath applying Gly1-SIFamide to the isolated STG also enhanced pyloric rhythm activity and activated an imperfectly coordinated gastric mill rhythm that included unusually prolonged bursts in two circuit neurons [inferior cardiac (IC), lateral posterior gastric (LPG)]. Furthermore, longer duration (>30 s) MCN5 stimulation activated a Gly1-SIFamide-like gastric mill rhythm, including prolonged IC and LPG bursting. The prolonged LPG bursting decreased the coincidence of its activity with neurons to which it is electrically coupled. We also identified local circuit feedback onto the MCN5 axon terminals, which may contribute to some distinctions between the responses to MCN5 stimulation and Gly1-SIFamide application. Thus, MCN5 adds to the few identified projection neurons that modulate a well-defined circuit at least partly via an identified neuropeptide transmitter and provides an opportunity to study peptide regulation of electrical coupled neurons in a functional context. NEW & NOTEWORTHY Limited insight exists regarding how identified peptidergic neurons modulate microcircuits. We show that the modulatory projection neuron modulatory commissural neuron 5 (MCN5) is peptidergic, containing Gly1-SIFamide. MCN5 and Gly1-SIFamide elicit similar output from two well-defined motor circuits. Their distinct actions may result partly from circuit feedback onto the MCN5 axon terminals. Their similar actions include eliciting divergent activity patterns in normally coactive, electrically coupled neurons, providing an opportunity to examine peptide modulation of electrically coupled neurons in a functional context.

scholarly journals Dynamic gain adjustments in descending corticofugal outputs from auditory cortex compensate for cochlear nerve synaptic damage

2017 ◽  
Author(s):  
Meenakshi M Asokan ◽  
Ross S Williamson ◽  
Kenneth E Hancock ◽  
Daniel B Polley
Keyword(s):  
Auditory Cortex ◽  
Auditory Nerve ◽  
Sound Level ◽  
Functional Coupling ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Axon Terminals ◽  
Growth Functions ◽  
Adult Mice ◽  
Dynamic Gain

AbstractLayer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a compensatory plasticity in L5 auditory cortex (ACtx) projection neurons with axons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We used widefield calcium imaging to monitor daily changes in sound processing from the dense plexus of corticocollicular (CCol) axon terminals in awake adult mice. CCol sound level growth functions were stable in control conditions but showed bi-phasic gain changes following damage to cochlear afferent synapses. Auditory nerve and CCol growth functions were sharply reduced hours after cochlear synaptopathy, but CCol response gain rebounded above baseline levels by the following day and remained elevated for 2 weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus.

Postnatal development of perisomatic GABAergic axon terminals on neurons projecting from area 17 to area 18 of the cat visual cortex

1999 ◽  
Vol 16 (1) ◽  
pp. 35-44 ◽  
Author(s):  
FERNANDO PÉREZ-CERDÁ ◽  
LUIS MARTÍNEZ-MILLÁN ◽  
CARLOS MATUTE
Keyword(s):  
Visual Cortex ◽  
Postnatal Development ◽  
Developmental Stages ◽  
Time Frame ◽  
Projection Neurons ◽  
Area 17 ◽  
Gamma Aminobutyric Acid ◽  
Area 18 ◽  
Axon Terminals ◽  
Cat Visual Cortex

We have studied the postnatal development of presumptive axon terminals (puncta) which were recognized by antibodies to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and were located on the somata of area 17 neurons projecting to the ipsilateral area 18 of the visual cortex in cats ranging from 7 days of age to adulthood. Projection neurons were retrogradely labeled by injection of horseradish peroxidase conjugated to wheat germ agglutinin into the ipsilateral area 18. These neurons were mainly pyramidal in shape at all the developmental stages examined and the adult distribution of labeled cells was reached by 21 days. Subsequent GABA postembedding immunohistochemistry using high-resolution light microscopy was carried out to study the development of GABAergic terminals on cell bodies of identified projecting neurons in layers II–III. At all ages examined, we found perisomatic GABAergic puncta on these cells. Their density showed a significant increase from postnatal days 7 to 45, and then remained largely constant through adulthood. Since GABAergic puncta are considered the light-microscopic correlate of GABAergic synaptic terminals, our results support the idea of a developmentally regulated increase in the inhibitory activity of local interneurons on area 17 pyramidal neurons projecting to area 18 in the cat visual cortex which occurs within the same time frame as that of the acquisition of the mature operation of these cells.

scholarly journals Optical control of retrogradely infected neurons using drug-regulated “TLoop” lentiviral vectors

2014 ◽  
Vol 111 (10) ◽  
pp. 2150-2159 ◽  
Author(s):  
Ali Cetin ◽  
Edward M. Callaway
Keyword(s):  
Gene Expression ◽  
Viral Vectors ◽  
Lentiviral Vectors ◽  
Transduction Efficiency ◽  
Projection Neurons ◽  
Gene Products ◽  
Transcription Activator ◽  
Axon Terminals ◽  
The Face ◽  
Rabies Glycoprotein

Many approaches that use viral vectors to deliver transgenes have limited transduction efficiency yet require high levels of transgene expression. In particular, infection via axon terminals is relatively inefficient but is a powerful means of achieving infection of specific neuron types. Combining this with optogenetic approaches requires high gene expression levels that are not typically achieved with nontoxic retrogradely infecting vectors. We generated rabies glycoprotein-pseudotyped lentiviral vectors that use a positive feedback loop composed of a Tet promoter driving both its own tetracycline-dependent transcription activator (tTA) (“TLoop”) and channelrhodopsin-2-YFP (ChR2YFP). We show that TLoop vectors strongly express proteins in a drug-controllable manner in neurons that project to injection sites within the mouse brain. After initial infection, the virus travels retrogradely, stably integrates into the host genome, and expresses gene products. The expression is robust and allows optogenetic studies of neurons projecting to the location of virus injection, as demonstrated by fluorescence-targeted intracellular recordings. ChR2YFP expression did not cause observable signs of toxicity and continued for up to 6 mo after infection. Expression can be reversibly blocked by administration of doxycycline, if necessary, for expression of gene products that might be more toxic. Overall, we present a system that will allow researchers to achieve high levels of gene expression even in the face of inefficient viral transduction. The particular vectors that we demonstrate may enhance efforts to gain a precise understanding of the contributions of specific types of projection neurons to brain function.

scholarly journals Different microcircuit responses to comparable input from one versus both copies of an identified projection neuron

2020 ◽  
Vol 223 (20) ◽  
pp. jeb228114
Author(s):  
Gabriel F. Colton ◽  
Aaron P. Cook ◽  
Michael P. Nusbaum
Keyword(s):  
Firing Rate ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Gastric Mill ◽  
Cancer Borealis ◽  
Axon Terminals ◽  
Commissural Neuron ◽  
Co Activation ◽  
Multiple Copies ◽  
Protraction Phase

ABSTRACTNeuronal inputs to microcircuits are often present as multiple copies of apparently equivalent neurons. Thus far, however, little is known regarding the relative influence on microcircuit output of activating all or only some copies of such an input. We examine this issue in the crab (Cancer borealis) stomatogastric ganglion, where the gastric mill (chewing) microcircuit is activated by modulatory commissural neuron 1 (MCN1), a bilaterally paired modulatory projection neuron. Both MCN1s contain the same co-transmitters, influence the same gastric mill microcircuit neurons, can drive the biphasic gastric mill rhythm, and are co-activated by all identified MCN1-activating pathways. Here, we determine whether the gastric mill microcircuit response is equivalent when stimulating one or both MCN1s under conditions where the pair are matched to collectively fire at the same overall rate and pattern as single MCN1 stimulation. The dual MCN1 stimulations elicited more consistently coordinated rhythms, and these rhythms exhibited longer phases and cycle periods. These different outcomes from single and dual MCN1 stimulation may have resulted from the relatively modest, and equivalent, firing rate of the gastric mill neuron LG (lateral gastric) during each matched set of stimulations. The LG neuron-mediated, ionotropic inhibition of the MCN1 axon terminals is the trigger for the transition from the retraction to protraction phase. This LG neuron influence on MCN1 was more effective during the dual stimulations, where each MCN1 firing rate was half that occurring during the matched single stimulations. Thus, equivalent individual- and co-activation of a class of modulatory projection neurons does not necessarily drive equivalent microcircuit output.

scholarly journals Epigenomic Diversity of Cortical Projection Neurons in the Mouse Brain

2020 ◽  
Author(s):  
Zhuzhu Zhang ◽  
Jingtian Zhou ◽  
Pengcheng Tan ◽  
Yan Pang ◽  
Angeline Rivkin ◽  
...  
Keyword(s):  
Single Cell ◽  
Cortical Neurons ◽  
Neuronal Cell ◽  
Cell Types ◽  
Molecular Properties ◽  
Projection Neurons ◽  
Long Distance ◽  
Cortical Projection ◽  
Axon Terminals ◽  
Projection Properties

SummaryNeuronal cell types are classically defined by their molecular properties, anatomy, and functions. While recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain, neuronal cell types are often studied out of the context of their anatomical properties. To better understand the relationship between molecular and anatomical features defining cortical neurons, we combined retrograde labeling with single-nucleus DNA methylation sequencing to link epigenomic properties of cell types to neuronal projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical (CC) and cortico-subcortical long-distance projections. Our results revealed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. Based on their epigenomes, intra-telencephalic (IT) cells projecting to different cortical targets could be further distinguished, and some layer 5 neurons projecting to extra-telencephalic targets (L5-ET) formed separate subclusters that aligned with their axonal projections. Such separation varied between cortical areas, suggesting area-specific differences in L5-ET subtypes, which were further validated by anatomical studies. Interestingly, a population of CC projection neurons clustered with L5-ET rather than IT neurons, suggesting a population of L5-ET cortical neurons projecting to both targets (L5-ET+CC). We verified the existence of these neurons by labeling the axon terminals of CC projection neurons and observed clear labeling in ET targets including thalamus, superior colliculus, and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.

scholarly journals Mediodorsal thalamus contributes to the timing of instrumental actions

2020 ◽  
Author(s):  
Nicholas Lusk ◽  
Warren H. Meck ◽  
Henry H. Yin
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Neural Circuit ◽  
Interval Timing ◽  
Projection Neurons ◽  
Production Task ◽  
Direct Role ◽  
Mediodorsal Thalamus ◽  
Temporal Production

AbstractThe perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key component of the limbic cortico-basal ganglia-thalamocortical loop. In this study we tested the role of the MD in timing, using an operant temporal production task in male mice. In this task, the expected timing of available rewards is indicated by lever pressing. Inactivation of the MD with muscimol produced rightward shifts in peak pressing on probe trials as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD also resulted in similar changes in timing. The observed effects were found to be independent of significant changes in movement. Our findings suggest that the MD is a critical component of the neural circuit for interval timing, without playing a direct role in regulating ongoing performance.Significance StatementThe mediodorsal nucleus of the thalamus (MD) is strongly connected with the prefrontal cortex and basal ganglia, areas which have been implicated in interval timing. Previous work has shown that the MD contributes to working memory and learning of action-outcome contingencies, but its role in behavioral timing is poorly understood. Using an operant temporal production task, we showed that inactivation of the MD significantly impaired timing behavior.

scholarly journals Distinct Microcircuit Response to Comparable Input from a Full and Partial Projection Neuron Population

2020 ◽  
Author(s):  
Gabriel F. Colton ◽  
Aaron P. Cook ◽  
Michael P. Nusbaum
Keyword(s):  
Firing Rate ◽  
Single Copy ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Gastric Mill ◽  
Cancer Borealis ◽  
Axon Terminals ◽  
Co Activation ◽  
Multiple Copies ◽  
Summary Statement

ABSTRACTNeuronal inputs to microcircuits are often present as multiple copies of apparently equivalent neurons. Thus far, however, little is known regarding the relative influence on microcircuit output of activating all or only some copies of such an input. We are examining this issue in the crab (Cancer borealis) stomatogastric ganglion, where the gastric mill (chewing) microcircuit is activated by MCN1, a paired modulatory projection neuron. Both MCN1s contain the same cotransmitters, influence the same gastric mill circuit neurons, can drive the biphasic gastric mill rhythm, and are co-activated by all identified MCN1-activating pathways. Here, we determine whether the gastric mill circuit response is equivalent when stimulating one or both MCN1s under conditions where the pair are matched to collectively fire at the same overall rate and pattern as single MCN1 stimulation. The dual MCN1 stimulations elicited more consistently coordinated rhythms, and these rhythms exhibited longer phases and cycle periods. These different outcomes from single and dual MCN1 stimulation may have resulted from the relatively modest, and equivalent, firing rate of the gastric mill neuron LG during each matched set of stimulations. The LG neuron-mediated, ionotropic inhibition of the MCN1 axon terminals is the trigger for the transition from the retraction to protraction phase. This LG neuron influence on MCN1 was more effective during the dual stimulations, where each MCN1 firing rate was half that occurring during the matched single stimulations. Thus, equivalent individual- and co-activation of a class of modulatory projection neurons will not necessarily drive equivalent microcircuit output.Summary StatementCo-stimulating both copies of an identified modulatory projection neuron at the same collective firing rate used for single copy stimulation results in distinct microcircuit output.

scholarly journals Perigenual and Subgenual Anterior Cingulate Afferents Converge on Common Pyramidal Cells in Amygdala Subregions

2021 ◽  
Author(s):  
Emily A Kelly ◽  
V. Kaye Thomas ◽  
Apoorva Indraghanty ◽  
Julie L Fudge
Keyword(s):  
Pyramidal Cells ◽  
Afferent Input ◽  
Social Contexts ◽  
Cellular Level ◽  
Anterior Cingulate ◽  
Projection Neurons ◽  
Conflict Monitoring ◽  
Basal Nuclei ◽  
Axon Terminals ◽  
Social Monitoring

The subgenual (sgACC) and pregenual (pgACC) anterior cingulate are important afferents of the amygdala, and have different cytoarchitecture, connectivity, and function. The sgACC is associated with arousal mechanisms linked to salient cues, while the pgACC is engaged in conflict decision-making, including in social contexts. How they influence the amygdala at the cellular level has not been explored in higher species. In monkeys, we placed same size, small volume tracer injections into sgACC and pgACC of the same hemisphere, and examined their terminal distribution to better understand how these different functional systems communicate with the amygdala. The sgACC has broad-based termination patterns in the amygdala, while the pgACC has a more restricted pattern which was always nested in sgACC terminals. Overlap of labeled fibers from each area occurred in subregions of the accessory basal and basal nuclei, termed 'hotspots'. In triple-labeling confocal studies, we found that the majority of randomly selected CAMIIα (+) cells (putative amygdala glutamatergic neurons) in 'hotspots' received dual contacts from the sgACC and pgACC. The ratio of dual contacts onto CAMIIα (+) cells occurred over a surprisingly narrow range in all 'hotspots', suggesting a consistent, tight balance of afferent contacts on postsynaptic projection neurons. We also found differences in bouton size from each afferent input. Large boutons, which are associated with greater synaptic strength, were approximately 3 times more frequent on sgACC versus pgACC axon terminals. Together, the results reveal a nested interaction in which pgACC ('conflict/social monitoring') terminals converge with the broader sgACC ('salience') terminals at both the mesoscopic and cellular level in 'hotspots', and do so in a tightly balanced manner. sgACC afferents have axonal bouton sizes consistent with a 'driver' function whereby new arousing cues (sgACC) can rapidly influence higher cognitive computations such as social/conflict monitoring.

scholarly journals Dopaminergic treatment weakens medium spiny neuron collateral inhibition in the parkinsonian striatum

2017 ◽  
Vol 117 (3) ◽  
pp. 987-999 ◽  
Author(s):  
Wei Wei ◽  
Shengyuan Ding ◽  
Fu-Ming Zhou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
D2 Receptor ◽  
Gaba Release ◽  
D1 Receptor ◽  
Medium Spiny Neuron ◽  
High Rate ◽  
Projection Neurons ◽  
Axon Terminals ◽  
Inhibitory Strength

The striatal medium spiny neurons (MSNs) are critical to both motor and cognitive functions. A potential regulator of MSN activity is the GABAergic collateral axonal input from neighboring MSNs. These collateral axon terminals are further under the regulation of presynaptic dopamine (DA) receptors that may become dysfunctional when the intense striatal DA innervation is lost in Parkinson's disease (PD). We show that DA D1 receptor-expressing MSNs (D1-MSNs) and D2 receptor-expressing MSNs (D2-MSNs) each formed high-rate, one-way collateral connections with a homotypic preference in both normal and DA-denervated mouse striatum. Furthermore, whereas the homotypic preference, one-way directionality and the basal inhibitory strength were preserved, DA inhibited GABA release at the D2-MSN→D2-MSN collateral synapse in a supersensitive manner in the DA-denervated striatum. In contrast, for D1-MSN-originated collateral connections, whereas D1 agonism facilitated D1-MSN→D1-MSN collateral inhibition in the normal striatum, this presynaptic D1R facilitation of GABA release was lost in the parkinsonian striatum. These results indicate that in the parkinsonian striatum, dopaminergic treatment can presynaptically weaken the D2-MSN→D2-MSN collateral inhibition and disinhibit the surrounding D2-MSNs, whereas the D1-MSN→D1-MSN collateral inhibition is weakened by the loss of the presynaptic D1 receptor facilitation, disinhibiting the surrounding D1-MSNs. Together, these newly discovered effects can disrupt the MSN circuits in the parkinsonian striatum and may contribute to dopaminergic treatment-induced aberrant motor and nonmotor behaviors in PD. NEW & NOTEWORTHY With the use of a large database, this study establishes that neighboring homotypic striatal spiny projection neurons have a 50% chance to form one-way collateral inhibitory connection, a substantially higher rate than previous estimates. This study also shows that dopamine denervation may alter presynaptic dopamine receptor function such that dopaminergic treatment of Parkinson's disease can weaken the surround inhibition and may reduce the contrast of the striatal outputs, potentially contributing to dopamine's profound motor and nonmotor behavioral effects.

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