Biology subjects

Haas, J. S.

Publications and source records attributed to Haas, J. S..

4 recordsLinked to original sources

bioRxiv2026

Synaptic GABA dysfunction of thalamocortical neurons impairs sleep spindle morphology and recovery from fearful memories.

The neural mechanisms which control the characteristic waxing and waning shape of sleep spindles and their dysregulation in neuropsychiatric illnesses are unresolved. Recent, sparse research shows post-traumatic stress disorder (PTSD) presents with abnormal spindle morphology and dysfunctional synaptic GABAA receptors in midline thalamic regions. We modeled this GABAA receptor dysfunction by localized CRISPR-Cas9-knockdown in mice. In contrast to a control group with intact GABAA receptors, mice with synaptic GABAA receptor knock-down in thalamocortical (TC) neurons lost the characteristic waxing and waning shape of sleep spindles and exhibited a failure to diminish conditioned contextual fear responses. Our results suggest that abnormally shaped sleep spindles may be a marker of synaptic GABA dysfunction in TC neurons and an indicator of disrupted fear extinction.

neuroscience↗

bioRxiv2025

Electrical coupling within thalamocortical networks cumulatively reduces cortical correlation to sensory inputs

Thalamocortical (TC) cells relay sensory information to the cortex, as well as driving their own feedback inhibition through collateral excitation of the thalamic reticular nucleus (TRN). The GABAergic cells of the TRN are extensively coupled through electrical synapses. While electrical synapses are most often noted for their roles in synchronizing rhythmic forms of neuronal activity, they are also positioned to modulate responses to transient information flow across and throughout the brain, although this effect is seldom explored. Here we sought to understand how electrical synapses embedded within a network of TRN neurons regulate the processing of ongoing sensory inputs during relay from thalamus to cortex. We used Hodgkin-Huxley point models to construct a network of a 9 TC and 9 TRN cells, with one cortical output neuron summing the TC activity. Each pair of TC and TRN cells was reciprocally coupled by chemical synapses. TRN cells were each electrically coupled to two neighboring cells, forming a ring topology. TC cells received synaptic inputs in sequence, with intervals between inputs varying from 10 to 50 ms across simulations. This architecture and sequence of inputs allowed us to assess the functional radius of an electrical synapse by comparing the cumulative effects of each additional TRN electrical synapse on the responses of the TRN and TC cells and the cortical output. Effects of electrical synapses on TRN cell activity were strongest for smaller intervals between inputs, and cumulative with additional synapses. In contrast, effects in TC neurons were strongest for larger intervals between inputs and also increased with coupling strength. Coupling within TRN modulated cortical integration of TC inputs by unexpectedly increasing response rates, duration and reducing spike correlation to the input sequence that was presented to the TC layer. Thus, embedded TRN electrical synapses exert powerful influence on thalamocortical relay, in a cumulative manner. These results highlight the multi-synaptic influences of electrically coupled cells and reinforce that they should be included in more complex and realistic networks of the brain.

neuroscience↗

bioRxiv2024

Cell-specific inhibitory modulation of sound processing in the auditory thalamus.

Inhibition plays an important role in controlling the flow and processing of auditory information throughout the central auditory pathway, yet how inhibitory circuits shape auditory processing in the medial geniculate body (MGB), the key region in the auditory thalamus, is poorly understood. The MGB gates the flow of auditory information to the auditory cortex, and it is inhibited largely by the thalamic reticular nucleus (TRN). The TRN contains two major classes of inhibitory neurons: parvalbumin (PVTRN)-positive and somatostatin (SSTTRN)-positive neurons. PV and SST neurons have been shown to play differential roles in controlling sound responses in auditory cortex. In the somatosensory and visual subregions of the TRN, PVTRN and SSTTRN neurons exhibit anatomical and functional differences. However, it remains unknown whether and how PVTRN and SSTTRN neurons differ in their anatomical projections from the TRN to the auditory thalamus, and whether and how they differentially modulate activity in the MGB. We find that PVTRN and SSTTRN neurons exhibit differential projection patterns within the auditory thalamus: PVTRN neurons predominantly project to ventral MGB, whereas SSTTRN neurons project to the dorso-medial regions of MGB. Optogenetic inactivation of PVTRN neurons bidirectionally modulated sound-evoked activity in MGB, increasing firing in 29% of MGB neurons, while suppressing firing in 41%. In contrast, inactivating SSTTRN neurons largely suppressed tone-evoked activity in MGB neurons. Cell type-specific computational models identified candidate circuit mechanisms for generating the differential effects of TRN inactivation on MGB sound responses. These distinct inhibitory pathways within the auditory thalamus reveal cell type-specific organization of thalamic inhibition in auditory computation.

neuroscience↗

bioRxiv2018

Electrical synapses regulate both subthreshold and population activity of principal cells in response to transient inputs within canonical feedforward circuits

As information about the world traverses the brain, the signals exchanged between neurons are passed and modulated by synapses, or specialized contacts between neurons. While neurotransmitter-based synapses tend to be either relay excitatory or inhibitory pulses of influence on the postsynaptic neuron, electrical synapses, composed of plaques of gap junction channels, are always-on transmitters that can either excite or inhibit a coupled neighbor. A growing body of evidence indicates that electrical synapses, similar to their chemical counterparts, are modified in strength during physiological neuronal activity. The synchronizing role of electrical synapses in neuronal oscillations has been well established, but their impact on transient signal processing in the brain is much less understood. Here we constructed computational models based on the canonical feedforward neuronal circuit, and included electrical synapses between inhibitory interneurons. We provided discrete closely-timed inputs to the circuits, and characterize the influence of electrical synapses on both the subthreshold summation and spike trains in the output neuron. Our simulations highlight the diverse and powerful roles that electrical synapses play even in simple circuits. Because these canonical circuits are represented widely throughout the brain, we expect that these are general principles for the influence of electrical synapses on transient signal processing across the brain.\n\nAuthor SummaryThe role that electrical synapses play in neural oscillations, network synchronization and rhythmicity is well established, but their role neuronal processing of transient inputs is much less understood. Here we used computational models of canonical feedforward circuits and networks to investigate how the strength of electrical synapses regulates the flow of transient signals passing through those circuits. We show that because the influence of electrical synapses on coupled neighbors can be either inhibitory or excitatory, their role in network information processing is heterogeneous.. Because of the widespread existence of electrical synapses between interneurons as well as a growing body of evidence for their plasticity, we expect such effects play a significant role in how the brain processes transient inputs.

neuroscience↗