GABAergic neurons

Effects of pathological Tau on hippocampal neuronal activity and spatial memory in ageing mice

The gradual accumulation of hyperphosphorylated forms of the Tau protein (pTau) in the human brain correlate with cognitive dysfunction and neurodegeneration. I will present our recent findings on the consequences of human pTau aggregation in the hippocampal formation of a mouse tauopathy model. We show that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to their neurodegeneration. In aged but not younger mice, pTau spreads to oligodendrocytes. During ‘goal-directed’ navigation, we detect fewer high-firing pyramidal cells, but coupling to network oscillations is maintained in the remaining cells. The firing patterns of individually recorded and labelled pyramidal and GABAergic neurons are similar in transgenic and non-transgenic mice, as are network oscillations, suggesting intact neuronal coordination. This is consistent with a lack of pTau in subcortical brain areas that provide rhythmic input to the cortex. Spatial memory tests reveal a reduction in short-term familiarity of spatial cues but unimpaired spatial working and reference memory. These results suggest that preserved subcortical network mechanisms compensate for the widespread pTau aggregation in the hippocampal formation. I will also briefly discuss ideas on the subcortical origins of spatial memory and the concept of the cortex as a monitoring device.

SCN1A/Nav1.1 sodium channel: loss and gain of function in epilepsy and migraine

Genetic mutations of the SCN1A gene, the voltage gated sodium channel NaV1.1, cause well-defined epilepsies, including the severe developmental and epileptic encephalopathy Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+), as well as a severe form of migraine with aura, familial hemiplegic migraine (FHM). More recently, they have been identified in an extremely severe early infantile encephalopathy. Functional studies and animal models have contributed to disclose pathological mechanisms, which can be often linked to a straightforward loss- vs gain- of channel function. However, although this simple dichotomy is pertinent and useful, detailed pathological mechanisms in neuronal circuits can be more complex, sometimes because of unexpected homeostatic or pathologic responses. I will compare pathological mechanisms of epilepsy and migraine mutations studied with cellular, animal and computational models, highlighting a novel homeostatic response implemented by CCK-positive GABAergic neurons in a mouse model of Dravet syndrome, which may be boosted in therapeutic approaches.

All optical interrogation of developing GABAergic circuits in vivo

The developmental journey of cortical interneurons encounters several activity-dependent milestones. During the early postnatal period in developing mice, GABAergic neurons are transient preferential recipients of thalamic inputs and undergo activity-dependent migration arrest, wiring and programmed cell-death. But cortical GABAergic neurons are also specified by very early developmental programs. For example, the earliest born GABAergic neurons develop into hub cells coordinating spontaneous activity in hippocampal slices. Despite their importance for the emergence of sensory experience, their role in coordinating network dynamics, and the role of activity in their integration into cortical networks, the collective in vivo dynamics of GABAergic neurons during the neonatal postnatal period remain unknown. Here, I will present data related to the coordinated activity between GABAergic cells of the mouse barrel cortex and hippocampus in non-anesthetized pups using the recent development of all optical methods to record and manipulate neuronal activity in vivo. I will show that the functional structure of developing GABAergic circuits is remarkably patterned, with segregated assemblies of prospective parvalbumin neurons and highly connected hub cells, both shaped by sensory-dependent processes.

Medial Septal GABAergic Neurons Reduce Seizure Duration Upon Wireless Optogenetic Closed-Loop Stimulation

Seizures can emerge from multiple or large foci in temporal lobe epilepsy (TLE), complicating focally targeted strategies such as surgical resection or the modulation of the activity of specific hippocampal neuronal populations through genetic or optogenetic techniques. Here, we evaluate a strategy in which optogenetic activation of medial septal GABAergic neurons (MSGNs), which provide extensive projections throughout the hippocampus, is used to control seizures. We found that MSGNs were structurally and functionally resilient in the chronic intrahippocampal kainate mouse model of TLE, which as is often the case in human TLE patients, presents with hippocampal sclerosis. Optogenetic stimulation of MSGNs modulated oscillations across the rostral to caudal extent of the hippocampus in epileptic conditions. Chronic wireless optogenetic stimulation of MSGNs, upon electrographic detection of spontaneous hippocampal seizures, resulted in reduced seizure durations. We propose MSGNs as a novel target for optogenetic control of seizures in TLE.

Contribution of GirK channels expressed in VTA GABAergic neurons to anxiety, social behaviors and hippocampal-dependent memory

Functional characterization of healthy and Alzheimer’s disease-related 3D neurospheres formed using human iPSC-derived glutamatergic neurons, GABAergic neurons, and astrocytes

FENS Forum 2024

mTOR pathway disruption in GABAergic neurons impacts morphological and functional development of cortical and thalamic somatosensory areas in a mouse model of autism spectrum disorder

FENS Forum 2024

Role of the medial amygdala glutamatergic and GABAergic neurons during social defeat

FENS Forum 2024

Pay attention to this change: Lateral Hypothalamic GABAergic neurons in attention and alcohol memories

Cognitive and emotional functions of mice lacking the mineralocorticoid receptor in glutamatergic or GABAergic neurons

Deletion of beta2 nicotinic subunit in specific types of cortical GABAergic neurons changes social and anxiety-like behavior

AAV delivery of shRNA against IRS1 in GABAergic neurons in rat hippocampus alters synaptic plasticity and impairs spatial memory in females and male rats

Dlx5/6 levels in mouse GABAergic neurons affect adult Parvalbumin-positive neuronal density and control anxiety/compulsive behaviours

Functional alteration of myelinated GABAergic neurons in the hippocampus of Contactin2- and 4.1B-deficient mice

GABAergic neurons of the posterior Nucleus Basalis modulate information processing in the auditory pathway

Involvement of parvalbumin-positive GABAergic neurons in basal forebrain modulation in a mouse model of neuropathic pain

How single GABAergic neurons shape local circuit dynamics: an all-optical approach

Thalamic projection GABAergic neurons: retinal input and function in vigilance state transitions

Transient developmental increase in cortical projections to amygdala GABAergic neurons contribute to circuit dysfunction following early life stress

In vivo direct reprogramming of OPCs into GABAergic neurons in adolescent and adult mouse brain

Basolateral amygdala parvalbumin and cholecystokinin-expressing GABAergic neurons modulate depressive and anxiety-like behaviors

FENS Forum 2024

Boosting as therapeutic approach a homeostatic response played by cholecystokinin (CCK)-positive basket GABAergic neurons in Scn1a+/- Dravet syndrome mice

FENS Forum 2024

Exploring the phenotypic impact of constitutive or late restoration of Nav1.1 in GABAergic neurons in a reversible mouse model of Dravet syndrome

FENS Forum 2024

GABAergic neurons in the rostromedial tegmental nucleus mediate transitions from REM sleep to arousal in mice

FENS Forum 2024

Impaired and diminished long-range GABAergic neurons as the major perturbation in a microdeletion model of human neuropsychiatric disorders

FENS Forum 2024

MicroRNA-34a from GABAergic neurons of the raphe contributes to its peripheral plasma level

FENS Forum 2024

Origins of GABAergic neurons migrating through the human and monkey marginal zone during midgestation

FENS Forum 2024

The role of GABAergic neurons in experience-dependent alterations of sensory representations in zebrafish forebrain

FENS Forum 2024

Three-dimensional structural analysis of GABAergic neurons in the mouse claustrum using tissue-clearing technology

FENS Forum 2024