Biology subjects

Kala, A.

Publications and source records attributed to Kala, A..

4 recordsLinked to original sources

bioRxiv2026

Local inhibitory topology dictates the spatial compartmentalization of hippocampal sharp-wave ripples

Hippocampal sharp-wave ripples (SWRs) are essential for memory consolidation and represent among the most synchronous oscillatory events in the brain. Yet, despite their capacity for widespread synchronization, SWRs frequently remain confined to discrete hippocampal domains, revealing a paradox between global coordination and local autonomy. Here, by analysing existing in vivo recordings with an experimentally constrained three-dimensional biophysical model, we show that inhibitory activity and inhibitory topology serve fundamentally distinct functions. Whereas perisomatic inhibition gates SWR generation and dendritic inhibition regulates the strength and spectral properties of ripple oscillations, the spatial organization of inhibitory connectivity establishes local computational domains that enable autonomous ripple generators to coexist. Together, our findings identify a spatial dimension of inhibition, in which inhibitory activity governs the emergence and dynamics of SWRs, while inhibitory topology determines their spatial organization and autonomy.

neuroscience↗

bioRxiv2026

Hippocampal tangential insertions of high-density silicone probes in head-fixed mice enhance spatial sampling

The hippocampus is a key structure within the medial temporal lobe which plays a central role in the formation and consolidation of declarative memories. Despite technological progress, a full understanding of hippocampal rhythms, neuronal population activity, and the underlying connectivity remains elusive, partly due to its complex morphology in a croissant-like shape which limits coronal and sagittal approaches. To address this limitation, we propose two different tangential insertions of high-density electrode probes (Neuropixels 1.0) aligned to either the dorsal or ventral sections of the hippocampus. Each approach enables the placement of up to 384 recording sites within the hippocampal formation. Both insertions are performed in head-fixed conditions, which can be easily combined with detailed monitoring of the animals behavioral states including spontaneous running and facial movements. The two proposed tangential dorsal and ventral insertions capture almost continuously the physiology of the hippocampus across 3.84 mm of tissue. We show that when placed across the pyramidal layer, such insertions can harness ripple oscillations from approximately 130 channels, corresponding to about [~]1.3 mm of tissue, with a coverage of 2 channels every 20 {micro}m. Furthermore, such insertions enabled us to record up to 400 hippocampal neurons simultaneously from a single probe, endowing us with the capability to capture putative functionally connected neuronal pairs. Although the conventional orthogonal/vertical approach is optimal for recording the laminar organization of hippocampal activity, we demonstrate how, for the longitudinal axis of hippocampus, tangential insertions can substantially increase spatial reach and sampling resolution, enabling a more detailed description of activity along this axis.

neuroscience↗

bioRxiv2024

LPS-induced sepsis disrupts brain activity in a region- and vigilance-state specific manner

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis and the systemic inflammatory response syndrome that leads to lasting consequences in survivors. It manifests as early EEG changes, that are region-, time- and state-specific, possibly reflecting distinct mechanisms of injury. Here, we investigated the effects of 5mg/kg lipopolysaccharide (LPS) on hippocampal and cortical sleep-wake states, oscillatory and non-oscillatory neuronal activity, as well as on within and between state dynamics using state-space analysis. LPS induced rapid-onset severe temporal and spatial vigilance state fragmentation, which preceded all other spectral changes by [~]90 minutes. Thereafter, LPS led to specific destabilization and increased delta oscillatory activity in wakefulness, but not NREM sleep, although state transitions remained largely normal. Instead, reduced NREM delta power resulted from aperiodic spectrum changes. LPS specifically reduced higher frequency hippocampal gamma oscillations (60-80Hz peak) in wakefulness, but not cortical high gamma or lower frequency gamma oscillations. These results suggest that disruption of sleep-wake patterns could serve as an early indicator of sepsis and associated encephalopathy, independent of spectral changes. Moreover, treatment aimed at stabilizing vigilance states in early stages of sepsis might prove to be a novel option preventing the development of further pathological neurophysiology, as well as limiting inflammation-related brain damage.

neuroscience↗

bioRxiv2022

Sepsis-induced brain state instability

Sepsis-associated brain dysfunction (SABD) is a frequent severe complication of sepsis and the systemic inflammatory response syndrome. It is associated with high mortality and a majority of survivors suffer long-term neurological consequences. Here, we aimed at better understanding the effects of SABD on oscillatory brain states in an acute rat model of sepsis induced by high dose LPS (10 mg/kg). To focus on intrinsically generated brain state dynamics, we used a urethane model that spares oscillatory activity in REM- and NREM-like sleep states. Soon after the intraperitoneal LPS injection we observed a robust instability of both oscillatory states resulting in tripling amount of state transitions that lasted for several hours, although the overall time spent in either state did not change. Analysis of power spectra showed opposing shifts in low frequency oscillations (1-9 Hz) that resulted in increased similarity between both states in 2-D state space. The described spectral characteristics of sepsis-induced EEG state instability might point to a mechanism underlying severe sleep fragmentation as described both in sepsis patients and in SABD animal models.

neuroscience↗