Biology subjects

Gillie, G. R.

Publications and source records attributed to Gillie, G. R..

3 recordsLinked to original sources

bioRxiv2026

Presynaptic control of top-down signaling in neocortical layer 1

The integration of bottom-up and top-down signals is crucial for perception and behavior. Neocortical layer 1 (L1) is a key target for top-down inputs and contains various GABAergic interneurons. Here, we investigated whether GABA can presynaptically regulate neurotransmitter release at top-down synapses targeting L1 of primary somatosensory cortex (S1). Our findings show that presynaptic GABAB receptor activation suppresses corticocortical inputs from primary motor (M1) and secondary somatosensory cortices (S2) more than those from the posterior medial nucleus of the thalamus (POm). This effect varied by target cell type, with GABAergic interneurons being less affected. Finally, we demonstrate that L1 neuron-derived neurotrophic factor (NDNF)-expressing interneurons inhibit top-down synapses more effectively than somatostatin-expressing interneurons, and that POm drives L1 neurogliaform cells, a subtype of NDNF interneuron that elicits unitary GABAB responses. These results reveal a novel circuit in which higher-order thalamus influences top-down corticocortical communication via L1 neurogliaform cells.

neuroscience↗

bioRxiv2024

Complimentary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments and neurobehavioral phenotypes including autism and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We first show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function in mice that will pave the way for future molecular studies into DESSH. These studies present two new animals that begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac.

neuroscience↗

bioRxiv2024

Functional dynamics and selectivity of two parallel corticocortical pathways from motor cortex to layer 5 circuits in somatosensory cortex

In the rodent whisker system, active sensing and sensorimotor integration are mediated in part by the dynamic interactions between the motor cortex (M1) and somatosensory cortex (S1). However, understanding these dynamic interactions requires knowledge about the synapses and how specific neurons respond to their input. Here, we combined optogenetics, retrograde labeling, and electrophysiology to characterize the synaptic connections between M1 and layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons in S1 of mice (both sexes). We found that M1 synapses onto IT cells displayed modest short-term depression, whereas synapses onto PT neurons showed robust short-term facilitation. Despite M1 inputs to IT cells depressing, their slower kinetics resulted in summation and a response that increased during short trains. In contrast, summation was minimal in PT neurons due to the fast time course of their M1 responses. The functional consequences of this reduced summation, however, were outweighed by the strong facilitation at these M1 synapses, resulting in larger response amplitudes in PT neurons than IT cells during repetitive stimulation. To understand the impact of facilitating M1 inputs on PT output, we paired trains of inputs with single backpropagating action potentials, finding that repetitive M1 activation increased the probability of bursts in PT cells without impacting the time-dependence of this coupling. Thus, there are two parallel but dynamically distinct systems of M1 synaptic excitation in L5 of S1, each defined by the short-term dynamics of its synapses, the class of postsynaptic neurons, and how the neurons respond to those inputs. SIGNIFICANCE STATEMENTNormal sensorimotor integration depends in part on the dynamic interactions between the primary motor cortex and the somatosensory cortex, but the functional properties of the excitatory synapses interconnecting the motor cortex with the somatosensory cortex are poorly understood. Our results show that the short-term dynamics of excitatory motor cortex synapses and the nature of the postsynaptic response they generate onto layer 5 pyramidal neurons in the somatosensory cortex depend on the postsynaptic cell type and if their axons project to other cortical areas or subcortical regions. These two parallel but dynamically distinct channels of synaptic excitation constitute previously unknown synaptic circuits by which different temporal patterns of motor cortex activity can shape how signals propagate out of the somatosensory cortex.

neuroscience↗