scholarly journals Cholinergic Midbrain Afferents Modulate Striatal Circuits and Shape Encoding of Action Control

2018 ◽  
Author(s):  
Daniel Dautan ◽  
Icnelia Huerta-Ocampo ◽  
Miguel Valencia ◽  
Krishnakanth Kondabolu ◽  
Todor V. Gerdjikov ◽  
...  
Keyword(s):  
Cognitive Flexibility ◽  
Acetylcholine Release ◽  
Cholinergic Neurons ◽  
Behavioral Adaptation ◽  
Projection Neurons ◽  
Cholinergic Transmission ◽  
Cholinergic Interneurons ◽  
Shape Encoding ◽  
Tegmental Nuclei ◽  
Excitatory Responses

SummaryAssimilation of novel strategies into a consolidated action repertoire is a crucial function for behavioral adaptation and cognitive flexibility. Acetylcholine in the striatum plays a pivotal role in such adaptation and its release has been causally associated with the activity of cholinergic interneurons. Here we show that the midbrain, a previously unknown source of acetylcholine in the striatum, is a major contributor to cholinergic transmission in the striatal complex. Neurons of the pedunculopontine and laterodorsal tegmental nuclei synapse with striatal cholinergic interneurons and give rise to excitatory responses that, in turn, mediate inhibition of spiny projection neurons. Inhibition of acetylcholine release from midbrain terminals in the striatum impairs action shifting and mimics the effects observed following inhibition of acetylcholine release from striatal cholinergic interneurons. These results suggest the existence of two hierarchically-organized modes of cholinergic transmission in the striatum where cholinergic interneurons are modulated by cholinergic neurons of the midbrain.

scholarly journals A selective projection from the subthalamic nucleus to parvalbumin-expressing interneurons of the striatum

2020 ◽  
Author(s):  
Krishnakanth Kondabolu ◽  
Natalie M. Doig ◽  
Olaoluwa Ayeko ◽  
Bakhtawer Khan ◽  
Alexandra Torres ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Ex Vivo ◽  
Cell Types ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Primary Input ◽  
Cholinergic Interneurons ◽  
Axonal Connections ◽  
Excitatory Responses

AbstractThe striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomical evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we carried out monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of ex vivo electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons is significantly higher (~ four-to eight-fold) than that from STN to any of the four other striatal cell types examined. In agreement, our recording experiments showed that parvalbumin-expressing interneurons, but not the other cell types tested, commonly exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs. Taken together, our data collectively demonstrate that the subthalamostriatal projection is highly selective for target cell type. We conclude that glutamatergic STN neurons are positioned to directly and powerfully influence striatal activity dynamics by virtue of their enriched innervation of GABAergic parvalbumin-expressing interneurons.

scholarly journals Cholinergic deficits selectively boost cortical intratelencephalic control of the striatum in Huntington’s disease

2021 ◽  
Author(s):  
Dalton Surmeier ◽  
Tristano Pancani ◽  
Michelle Day ◽  
Tatiana Tkatch ◽  
David Wokosin ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Acetylcholine Release ◽  
Pyramidal Tract ◽  
Projection Neurons ◽  
Mutant Huntingtin ◽  
Indirect Pathway ◽  
Cholinergic Interneurons ◽  
Triplet Expansion ◽  
Knockin Mouse

Abstract Huntington’s disease (HD) is a progressive, neurodegenerative disease caused by a CAG triplet expansion in the huntingtin gene. Although corticostriatal dysfunction has long been implicated in HD, the determinants and pathway specificity of this pathophysiology remain a matter of speculation. To help fill this gap, the zQ175+/- knockin mouse model of HD was studied using approaches that allowed optogenetic interrogation of intratelencephalic (IT) and pyramidal tract (PT) connections with principal striatal spiny projection neurons (SPNs). These studies revealed that the connectivity of IT, but not PT, neurons with direct and indirect pathway SPNs increased in early symptomatic zQ175+/- HD mice. This enhancement was attributable to reduced inhibitory control of IT terminals by striatal cholinergic interneurons (ChIs). Lowering mutant huntingtin selectively in ChIs with a virally-delivered zinc finger repressor protein normalized striatal acetylcholine release and IT functional connectivity – revealing a novel node in the network underlying corticostriatal pathophysiology in HD.

CONTEXTUAL LEARNING IN THE MORRIS WATER MAZE

2018 ◽  
pp. 13-20
Author(s):  
Е.И. Захарова ◽  
З.И. Сторожева ◽  
А.Т. Прошин ◽  
М.Ю. Монаков ◽  
А.М. Дудченко
Keyword(s):  
Morris Water Maze ◽  
Choline Acetyltransferase ◽  
Water Maze ◽  
Synaptic Membranes ◽  
Projection Neurons ◽  
Synaptic Organization ◽  
Acetyltransferase Activity ◽  
Cholinergic Interneurons ◽  
Late Stages ◽  
Choline Acetyltransferase Activity

Цель - исследование холинергической синаптической организации функций обучения и памяти у крыс с разными когнитивными способностями. Методы. Крыс обучали на пространственной обстановочной модели в водном лабиринте Морриса. Через 2-3 сут. после окончания тренировок животных декапитировали, из неокортекса и гиппокампа с помощью центрифугирования выделяли субфракции синаптических мембран и синаптоплазмы легких и тяжелых синаптосом. В синаптических субфракциях определяли активность ключевого фермента холинергических нейронов холинацетилтрансферазы (ХАТ). Сравнивали результаты тестирования (время достижения скрытой платформы) и активность фермента у способных и неспособных к обучению крыс. Результаты. Были выявлены: 1) различия в холинергической организации исследованных функций в процессе обучения у способных и неспособных к обучению крыс, в том числе: положительные корреляции активности ХАТ в синапсах проекционных нейронов неокортекса у способных крыс со временем достижения платформы на промежуточных этапах обучения и в синапсах проекционных нейронов гиппокампа у неспособных крыс на позднем этапе обучения; разнонаправленные корреляции активности ХАТ в синапсах, предположительно, интернейронов гиппокампа (фракция тяжелых синаптосом) у способных и неспособных крыс на начальном и позднем этапах обучения; 2) индивидуальность холинергической организации функций на всех этапах обучения. Выводы. Полученные данные свидетельствуют в пользу представлений о специфике холинергической организации функций пространственного обстановочного обучения у крыс с выраженными и слабыми способностями к обучению, а также избирательной роли холинергических интернейронов гиппокампа на исходном этапе обучения и в консолидации памяти. In order to expand the knowledge about neuronal organization of the cognitive functions required for understanding plastic processes in the brain, we investigated the cholinergic synaptic organization of learning and memory functions in rats with different cognitive abilities. Methods. Rats were trained on a contextual situation model in the Morris water maze. At 2-3 days after the end of training, animals were decapitated, and subfractions of synaptic membranes and synaptoplasm of light and heavy synaptosomes were isolated from the cortex and the hippocampus by centrifugation. In synaptic subfractions, activity of the key enzyme of cholinergic neurons, choline acetyltransferase, was measured. We compared the test results (latent period to reach the hidden platform) and the enzyme activity in capable (lower quartile) and incapable of learning rats (upper quartile). Results. The following was found: 1) differences in the cholinergic organization of studied functions in capable and uncapable of learning rats during training, including: positive correlations of choline acetyltransferase activity in synapses of projection neurons in the cortex of capable rats with latency to reach the platform at intermediate stages of training and in the hippocampus ofincapable rats at late stages of training; multidirectional correlations of choline acetyltransferase activity in synapses of hippocampal, presumably, interneurons (heavy synaptosomes) in capable and incapable rats at early and late stages of training; 2) distinctness of the cholinergic organization of functions at all stages of training. Conclusions. The study demonstrated for the first time a specificity of the cholinergic organization of functions in spatial situational learning of rats with strong and poor learning abilities and a selective role of hippocampal cholinergic interneurons at the initial stage of learning and in memory consolidation.

scholarly journals Tonic engagement of nicotinic receptors bidirectionally controls striatal spiny projection neuron spike timing

2021 ◽  
Author(s):  
Lior Matityahu ◽  
Jeffrey Malgady ◽  
Meital Schirelman ◽  
Yvonne Johansson ◽  
Jennifer Wilking ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Gaba Release ◽  
Projection Neuron ◽  
Spike Timing ◽  
Projection Neurons ◽  
Striatal Slices ◽  
Cholinergic Interneurons ◽  
Α7 Nachr ◽  
Α7 Nachrs

Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can 1) disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs and 2) directly modulate corticostriatal synaptic strength via pre-synaptic α7 nAChR receptors. Measurements of the disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that do not respond to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices we show that upon synchronous optogenetic activation of corticostriatal projections, blockade of α7 nAChRs delayed SPN spikes, whereas blockade of α4β2 nAChRs advanced SPN spikes and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond to phasic CIN activation. In particular, the observed spike-advancement caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, and a parallel hyperpolarization of PV-FSIs. Taken together, we describe opposing roles for tonic (as opposed to phasic) engagement of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs both sharpens the temporal fidelity of corticostriatal signaling via pre-synaptic α7 nAChRs and maintains a GABAergic brake on cortically-driven striatal output, processes that may shape SPN spike timing, striatal processing and synaptic plasticity.

scholarly journals Preferential cholinergic excitation of corticopontine neurons

2017 ◽  
Author(s):  
Arielle L. Baker ◽  
Ryan J. O’Toole ◽  
Allan T. Gulledge
Keyword(s):  
Pyramidal Neurons ◽  
Projection Neurons ◽  
Triggered Release ◽  
Calcium Dependent ◽  
M Current ◽  
Cation Conductance ◽  
Specific Selectivity ◽  
Ionic Mechanisms ◽  
Excitatory Responses ◽  
And Behavior

AbstractPyramidal neurons in layer 5 of the neocortex comprise two broad classes of projection neurons: corticofugal neurons, including corticopontine (CPn) neurons, and intratelencephalic neurons, including commissural/callosal (COM) neurons. These non-overlapping neuron subpopulations represent discrete cortical output channels contributing to perception, decision making, and behavior. CPn and COM neurons have distinct morphological and physiological characteristics, and divergent responses to modulatory transmitters such as serotonin and acetylcholine (ACh). To better understand how ACh regulates cortical output, in slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron subtypes, exogenous ACh generated qualitatively similar biphasic responses in which brief hyperpolarization was followed by longer-lasting enhancement of excitability. However, cholinergic inhibition was more pronounced in COM neurons, while excitatory responses were larger and longer lasting in CPn neurons. Similarly, optically triggered release of endogenous ACh from cholinergic terminals preferentially and persistently (for ~40 s) enhanced the excitability of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of CPn neurons involved at least three distinct ionic mechanisms: activation of a calcium-sensitive but calcium-permeable nonspecific cation conductance, suppression of Kv7 channels (the “M-current”), and activation of the calcium-dependent nonspecific cation conductance underlying afterdepolarizations. Our results demonstrate projection-specific selectivity in cholinergic signaling in the PFC, and suggest that transient release of ACh during behavior will preferentially promote corticofugal output.

Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord

2020 ◽  
Author(s):  
Mor R. Alkaslasi ◽  
Zoe E. Piccus ◽  
Hanna Silberberg ◽  
Li Chen ◽  
Yajun Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Rna Sequencing ◽  
Motor Neurons ◽  
Cholinergic Neurons ◽  
Functional Roles ◽  
Cholinergic Interneurons ◽  
Rich Diversity ◽  
Degenerative Disorders ◽  
Nuclear Rna ◽  
Single Nucleus

AbstractIn vertebrates, motor control relies on cholinergic neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these neurons and their different functional roles in the adult remain to be defined. Here, we developed a targeted single nuclear RNA sequencing approach and used it to identify an array of cholinergic interneurons, visceral and skeletal motor neurons. Our data expose markers for distinguishing these classes of cholinergic neurons and their extremely rich diversity. Specifically, visceral motor neurons, which provide autonomic control, could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor neurons was also reflected in our analysis with alpha, beta, and gamma subtypes clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.

Cholinergic Modulation of Purinergic and GABAergic Co-Transmission at In Vitro Hypothalamic Synapses

2002 ◽  
Vol 88 (5) ◽  
pp. 2501-2508 ◽  
Author(s):  
Young-Hwan Jo ◽  
Lorna W. Role
Keyword(s):  
In Vitro Release ◽  
Gaba Release ◽  
Synaptic Activity ◽  
Gabaergic Transmission ◽  
Sensory Pathways ◽  
Cholinergic Interneurons ◽  
Purinergic Transmission ◽  
Important Center ◽  
Tegmental Nuclei

The lateral hypothalamus (LH) is an important center for the integration of autonomic and limbic information and is implicated in the modulation of visceral motor and sensory pathways, including those underlying feeding and arousal behaviors. LH neurons in vitro release both ATP and GABA. The control of ATP and GABA co-transmission in LH may underlie the participation of LH in basic aspects of arousal and reinforcement. LH neurons receive cholinergic input from the pedunculopontine and laterodorsal tegmental nuclei as well as from cholinergic interneurons within the LH per se. This study presents evidence for nicotinic acetylcholine receptor (nAChR)-mediated enhancement of GABAergic, but not of purinergic, transmission despite the co-transmission of ATP and GABA at LH synapses in vitro. Facilitation of GABAergic transmission by nicotine is inhibited by antagonists of (αβ)*-containing nAChRs, but is unaffected by an α7-selective antagonist, consistent with a nAChR-mediated enhancement of GABA release mediated by non-α7-containing nAChRs. Activation of muscarinic ACh receptors enhances the release of ATP while concomitantly depressing GABAergic transmission. The independent modulation of ATP/GABAergic transmission may provide a new level of synaptic flexibility in which individual neurons utilize more than one neurotransmitter but retain independent control over their synaptic activity.

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