thalamic nucleus

Organization of thalamic networks and mechanisms of dysfunction in schizophrenia and autism

Thalamic networks, at the core of thalamocortical and thalamosubcortical communications, underlie processes of perception, attention, memory, emotions, and the sleep-wake cycle, and are disrupted in mental disorders, including schizophrenia and autism. However, the underlying mechanisms of pathology are unknown. I will present novel evidence on key organizational principles, structural, and molecular features of thalamocortical networks, as well as critical thalamic pathway interactions that are likely affected in disorders. This data can facilitate modeling typical and abnormal brain function and can provide the foundation to understand heterogeneous disruption of these networks in sleep disorders, attention deficits, and cognitive and affective impairments in schizophrenia and autism, with important implications for the design of targeted therapeutic interventions

Subthalamic nucleus

Integrative Neuromodulation: from biomarker identification to optimizing neuromodulation

Why do we make decisions impulsively blinded in an emotionally rash moment? Or caught in the same repetitive suboptimal loop, avoiding fears or rushing headlong towards illusory rewards? These cognitive constructs underlying self-control and compulsive behaviours and their influence by emotion or incentives are relevant dimensionally across healthy individuals and hijacked across disorders of addiction, compulsivity and mood. My lab focuses on identifying theory-driven modifiable biomarkers focusing on these cognitive constructs with the ultimate goal to optimize and develop novel means of neuromodulation. Here I will provide a few examples of my group’s recent work to illustrate this approach. I describe a series of recent studies on intracranial physiology and acute stimulation focusing on risk taking and emotional processing. This talk highlights the subthalamic nucleus, a common target for deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder. I further describe recent translational work in non-invasive neuromodulation. Together these examples illustrate the approach of the lab highlighting modifiable biomarkers and optimizing neuromodulation.

Targeting thalamic circuits rescues motor and mood deficits in PD mice

Although bradykinesia, tremor, and rigidity are hallmark motor defects in Parkinson’s disease (PD) patients, they also experience motor learning impairments and non-motor symptoms such as depression. The neural basis for these different PD symptoms are not well understood. While current treatments are effective for locomotion deficits in PD, therapeutic strategies targeting motor learning deficits and non-motor symptoms are lacking. We found that distinct parafascicular (PF) thalamic subpopulations project to caudate putamen (CPu), subthalamic nucleus (STN), and nucleus accumbens (NAc). While PF-->CPu and PF-->STN circuits are critical for locomotion and motor learning respectively, inhibition of the PF-->NAc circuit induced a depression-like state. While chemogenetically manipulating CPu-projecting PF neurons led to a long-term restoration of locomotion, optogenetic long-term potentiation at PF-->STN synapses restored motor learning behavior in PD model mice. Furthermore, activation of NAc-projecting PF neurons rescued depression-like PD phenotypes. Importantly, we identified nicotinic acetylcholine receptors capable of modulating PF circuits to rescue different PD phenotypes. Thus, targeting PF thalamic circuits may be an effective strategy for treating motor and non-motor deficits in PD.

Clinical and genetic predictors of subthalamic nucleus deep brain stimulation in Parkinson’s disease

Contextual modulation of cortical processing by a higher-order thalamic input

Higher-order thalamic nuclei have extensive connections with various cortical areas. Yet their functionals roles remain not well understood. In our recent studies, using optogenetic and chemogenetic tools we manipulated the activity of a higher-order thalamic nucleus, the lateral posterior nucleus (LP, analogous to the primate pulvinar nucleus) and its projections and examined the effects on sensory discrimination and information processing functions in the cortex. We found an overall suppressive effect on layer 2/3 pyramidal neurons in the cortex, resulting in enhancements of sensory feature selectivities. These mechanisms are in place in contextual modulation of cortical processing, as well as in cross-modality modulation of sensory processing.

Modulation of Visual Cortical Processing by a Higher-Order Thalamic Nucleus

The thalamus that speaks to the cortex: spontaneous activity in the developing brain

Our research team runs several related projects studying the cellular and molecular mechanisms involved in the development of axonal connections in the brain. In particular, our aim is to uncover the principles underlying thalamocortical axonal wiring, maintenance and ultimately the rewiring of connections, through an integrated and innovative experimental programme. The development of the thalamocortical wiring requires a precise topographical sorting of its connections. Each thalamic nucleus receives specific sensory information from the environment and projects topographically to its corresponding cortical. A second level of organization is achieved within each area, where thalamocortical connections display an intra-areal topographical organization, allowing the generation of accurate spatial representations within each cortical area. Therefore, the level of organization and specificity of the thalamocortical projections is much more complex than other projection systems in the CNS. The central hypothesis of our laboratory is that thalamocortical input influences and maintains the functional architecture of the sensory cortices. We also believe that rewiring and plasticity events can be triggered by activity-dependent mechanisms in the thalamus. Three major questions are been focused in the laboratory: i) the role of spontaneous patterns of activity in thalamocortical wiring and cortical development, ii) the role of the thalamus and its connectivity in the neuroplastic cortical changes following sensory deprivation, and iii) reprogramming thalamic cells for sensory circuit restoration. Within these projects we are using several experimental programmes, these include: optical imaging, manipulation of gene expression in vivo, cell and molecular biology, biochemistry, cell culture, sensory deprivation paradigms and electrophysiology. The results derived from our investigations will contribute to our understating of how reprogramming of cortical wiring takes place following brain damage and how cortical structure is maintained.

Compulsive-like seeking behavior correlates with AMPA receptor rectification in synapses of the subthalamic nucleus in a rat model of cocaine addiction

FENS Forum 2024

The subthalamic nucleus hyperdirect pathway neural dynamics during cocaine use and 'natural' reward seeking behavior – a pilot study

FENS Forum 2024

Behavioral and electrophysiological characterization of different functional regions of the subthalamic nucleus in healthy non-human primates

Cerebellar modulation of sensory processing through a higher order thalamic nucleus

Experimental investigation into the role of the subthalamic nucleus (STN) using optogenetics in mice

FOXP1 and nNOS neuronal populations in the adult human, mouse and rat subthalamic nucleus

Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats

Input-output relationships of the parafascicular thalamic nucleus in the mouse

Investigating the electrical stimulation of subthalamic nucleus for the treatment of cortical stroke

Molecular markers of the prenatal human subthalamic nucleus

Post-stress activity of calretinin positive cells in the paraventricular thalamic nucleus underlies long term, stress induced disturbance of behavior

Relationship between tonic dopamine level and aperiodic component from local field potentials of the subthalamic nucleus in hemiparkinsonian rats

Reversing escalated cocaine intake with social contact and optogenetic modulation of the subthalamic nucleus

Subthalamic nucleus deep brain stimulation reduces alcohol intake in rats under influence of proximal social factors

Convergence and segregation of afferents in the paraventricular thalamic nucleus

FENS Forum 2024

Differential expression of Cx36 in the reticulo-thalamic nucleus and hippocampus in a rat model of Parkinson's disease

FENS Forum 2024

Excitatory and inhibitory inputs of the paraventricular thalamic nucleus

FENS Forum 2024

Glutamatergic neurons in the subthalamic nucleus regulate arousal and REM sleep

FENS Forum 2024

Impact of aversive experiences on the reticular thalamic nucleus of mice

FENS Forum 2024

Interactions between the subthalamic nucleus and the primary motor cortex control parkinsonian motor and nociceptive disorders

FENS Forum 2024

Investigating the role of the subparafascicular thalamic nucleus in the processing of soft touch sensation in mice

FENS Forum 2024

Local activation of RCB1 suppresses burst firing of neurons in the reticular thalamic nucleus

FENS Forum 2024

A midline thalamic nucleus promotes compulsive-like self-grooming in rodents

FENS Forum 2024

Pathological delta oscillation in the subthalamic nucleus of rats with acute stroke relates to motor disability

FENS Forum 2024

Pathology of the subthalamic nucleus in Parkinson’s disease

FENS Forum 2024

Subpopulation of thalamic neurons possesses distinct anatomical connectivities and electrophysiological properties in the anterior thalamic nucleus

FENS Forum 2024

The subthalamic nucleus controls nociceptive integration in the spinal cord and reverses nociceptive hypersensitivity in Parkinson’s disease

FENS Forum 2024

Subthalamic nucleus optogenetic inhibition reduces motivation for social interactions

FENS Forum 2024