The striatum receives major excitatory inputs from the cortex and thalamus that predominantly target spines of medium-sized spiny neurons (MSNs). We aimed to determine whether there is any selectivity these two afferents in their innervation direct indirect pathway MSNs. To address this, we used bacterial artificial chromosome transgenic mice, which enhanced green fluorescent protein (EGFP) reports presence D 1 or 2 dopamine receptor subtypes, markers MSNs, respectively. Excitatory were...

The synucleins (α, β, and γ) are highly homologous proteins thought to play a role in regulating neurotransmission found abundantly presynaptic terminals. To overcome functional overlap between synuclein understand their signaling from mesostriatal dopaminergic neurons, we produced mice lacking all three members of the family. effect on system was assessed adult (4- 14-month-old) animals using combination behavioral, biochemical, histological, electrochemical techniques. Adult...

Transcriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that potential contributions of two GABAergic GPe to voluntary action fated from early life be distinct. Prototypic neurons derive medial ganglionic eminence embryonic subpallium and express transcription factor Nkx2-1. These fire at high rates alert rest, encode...

Retrieving and acting on memories of food-predicting environments are fundamental processes for animal survival. Hippocampal pyramidal cells (PYRs) the mammalian brain provide mnemonic representations space. Yet substrates by which these hippocampal support memory-guided behavior remain unknown. Here, we uncover a direct connection from dorsal CA1 (dCA1) hippocampus to nucleus accumbens (NAc) that enables behavioral manifestation place-reward memories. By monitoring neuronal ensembles in...

Cholinergic interneurons are key components of striatal microcircuits. In primates, tonically active neurons (putative cholinergic interneurons) exhibit multiphasic responses to motivationally salient stimuli that mirror those midbrain dopamine and together these two systems mediate reward-related learning in basal ganglia circuits. Here, we addressed the potential contribution cortical thalamic excitatory inputs characteristic vivo . We first recorded labeled individual anesthetized rats....

The striatum is comprised of medium-sized spiny projection neurons (MSNs) and several types interneuron, receives massive glutamatergic input from the cerebral cortex. Understanding striatal function requires definition electrophysiological properties neurochemically identified interneurons sampled in same context ongoing cortical activity vivo. To address this, we recorded firing cholinergic (expressing choline acetyltransferase; ChAT) GABAergic expressing parvalbumin (PV) or nitric oxide...

Mutations in LRRK2 are the most common cause of autosomal dominant Parkinson's disease, and relevance to sporadic form disease is becoming ever more apparent. It therefore essential that studies conducted improve our understanding cellular role this protein. Here we use multiple models techniques identify pathways through which mutations may lead development disease.

Abstract Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in TSC1 or TSC2 , which encode proteins that negatively regulate mTOR complex 1 (mTORC1). TSC associated with significant cognitive, psychiatric, and behavioral problems, collectively termed TSC-Associated Neuropsychiatric Disorders (TAND), the cell types responsible for these manifestations are largely unknown. Here we use type-specific Tsc1 deletion to test whether dopamine neurons, modulate...

Abstract Striatal dopamine (DA) is critical for action and learning. Recent data show that DA release under tonic inhibition by striatal GABA. Ambient GABA tone on projection neurons can be determined plasma membrane uptake transporters (GATs) located astrocytes neurons. However, whether GATs determine output are unknown. We reveal in mouse dorsolateral striatum, but not nucleus accumbens core, governed GAT-1 GAT-3. These partly localized to astrocytes, enriched striatum compared core. In a...

<title>Abstract</title> Lewy-bodies are protein aggregates that thought to lead neurodegeneration in Parkinson’s disease. However, little is known about the contributions of these symptomatology We injected alpha-synuclein pre-formed fibrils (PFFs) into dorsolateral striatum induce Lewy-like substantia nigra dopamine neurons and examined effects 1- 3-months post-injection, stages prior overt cell loss. Aggregate-bearing exhibited an increase burst-firing <italic>in vivo</italic> their firing...

Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping output. Schemes basal ganglia circuit dynamics generally consider PV+ be homogenous, despite considerable heterogeneity in both form and function. We demonstrate that selective co-expression another calcium-binding protein, secretagogin (Scgn), separates rat primate striatum into two topographically-, physiologically-...

Parkinson's disease (PD) is characterized by the death of dopamine neurons in substantia nigra pars compacta (SNc) and accumulation α-synuclein. Impaired autophagy has been implicated activation proposed as a treatment strategy. We generate human α-synuclein-expressing mouse model PD with macroautophagic failure to understand interaction between impaired macroautophagy find that generates p62-positive inclusions progressive neuron loss SNc. Despite this parkinsonian pathology, motor...

Abstract Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs govern release via nicotinic acetylcholine...

The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of basal ganglia. Projection neurons both STN can extensively interact with other ganglia nuclei, there is growing anatomic evidence direct axonal connections from striatum. There remains, however, a pressing need elucidate organization impact these subthalamostriatal projections in context diverse cell types constituting To address this, we conducted monosynaptic retrograde tracing genetically-defined...

SUMMARY Astrocytes are increasingly thought to have underestimated and important roles in modulating neuronal circuits. striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs govern release via nicotinic acetylcholine receptors...

Abstract The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of basal ganglia. Projection neurons both STN can extensively interact with other ganglia nuclei, there is growing anatomical evidence direct axonal connections from striatum. There remains, however, a pressing need elucidate organization impact these subthalamostriatal projections in context diverse cell types constituting To address this, we carried out monosynaptic retrograde tracing...

Retrieving and acting upon memories of food-predicting environments are essential for survival. Pyramidal cells (PYRs) in dorsal CA1 hippocampus (dCA1) the mammalian brain provide mnemonic representations space. While dCA1 PYRs cannot directly access motor centers, substrates by which these internal guide appetitive behavior unknown. Here, we uncover a circuit motif embedded nucleus accumbens (NAc) that enables behavioral readout reward-place memories. By monitoring neuronal ensemble...

The release of dopamine from axons is critical for normative brain function and behaviour. Impaired or otherwise inappropriate often correlates with changes in the ultrastructure neuron that can assessed electron microscopy. Here, we provide two protocols be used serially to, first, help user process animal tissue microscopy and, secondly, undertake quantitative analyses ultrastructural features dopaminergic axon terminals brain. This Protocol #1 describes how to prepare tissue, carry out...

The release of dopamine from axons is critical for normative brain function and behaviour. Impaired or otherwise inappropriate often correlates with changes in the ultrastructure neuron that can assessed electron microscopy. Here, we provide two protocols be used serially to, first, help user process animal tissue microscopy and, secondly, undertake quantitative analyses ultrastructural features dopaminergic axon terminals brain. Protocol #1 describes how to prepare tissue, carry out...

The release of dopamine from axons is critical for normative brain function and behaviour. Impaired or otherwise inappropriate often correlates with changes in the ultrastructure neuron that can assessed electron microscopy. Here, we provide two protocols be used serially to, first, help user process animal tissue microscopy and, secondly, undertake quantitative analyses ultrastructural features dopaminergic axon terminals brain. This Protocol #1 describes how to prepare tissue, carry out...