Biology subjects

Bolding, K. A.

Publications and source records attributed to Bolding, K. A..

5 recordsLinked to original sources

bioRxiv2026

Aging reshapes odor-evoked dynamics in central olfactory circuits

Olfactory decline is among the earliest signs of aging and predicts later cognitive decline and neurodegenerative disease. Age-related impairments in odor identification and discrimination implicate central olfactory brain regions in both mice and humans, but it remains unclear where in the processing hierarchy aging alters neural function relating to these cognitive and perceptual deficits. To resolve this, we acquired simultaneous Neuropixels recordings from olfactory bulb (OB) and piriform cortex (PCx) in young and old mice during awake, head-fixed odor presentation, allowing us to probe multiple levels of odor response features within each animal. Our recordings revealed a shift toward greater excitation in both regions and reduced inhibitory neuron activity in PCx. Aging also restructured odor-evoked local field potential (LFP) oscillations within and across regions, with strongly elevated beta power and coherence. Population odor representations were less discriminable in OB, but not in PCx. Thus, our results point to reduced discriminability of OB population odor representations as the clearest neural analog of previously reported discrimination deficits. Single-unit, LFP, and population measures did not collapse onto a single axis using dimensionality reduction, indicating that several partly independent processes reshape the dynamics of odor responses in central olfactory circuits with aging. Together, these findings identify central circuit excitation/inhibition (E/I) and oscillatory imbalances that parallel age-related olfactory dysfunction despite largely preserved odor responsivity.

neuroscience↗

bioRxiv2021

Large-scale cellular-resolution imaging of neural activity in freely behaving mice

Miniaturized microscopes for head-mounted fluorescence imaging are powerful tools for visualizing neural activity during naturalistic behaviors, but the restricted field of view of first-generation miniscopes limits the size of neural populations accessible for imaging. Here we describe a novel miniaturized mesoscope offering cellular-resolution imaging over areas spanning several millimeters in freely moving mice. This system enables comprehensive visualization of activity across entire brain regions or interactions across areas.

neuroscience↗

bioRxiv2019

Pattern recovery by recurrent circuits in piriform cortex

Pattern completion, or the ability to retrieve stable neural activity patterns from noisy or partial cues, is a fundamental feature of memory. Theoretical studies indicate that recurrently connected auto-associative or discrete attractor network models can perform this process. Although phenomenological evidence for pattern completion and attractor dynamics have been described in various recurrent neural circuits, the crucial role that recurrent circuitry plays in implementing these processes has not been shown. Here we show that although odor representations in mouse olfactory bulb degrade under anesthesia, responses in downstream piriform cortex remain robust. Recurrent connections are required to stabilize cortical odor representations across states. Moreover, piriform odor representations exhibit attractor dynamics, both within and across trials, and these are also abolished when recurrent circuitry is eliminated. Thus, an auto-associative cortical circuit stabilizes output in response to degraded input, and the recurrent circuitry that defines these networks is required for this stabilization.

neuroscience↗

bioRxiv2018

Place cell firing cannot support navigation without intact septal circuits

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: tetracaine, a local anesthetic; muscimol, a GABA-A agonist; and gabazine, a GABA-A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rats ability to navigate to a hidden goal. After gabazine, location specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.

neuroscience↗

bioRxiv2018

Recurrent cortical circuits implement concentration-invariant odor coding

Animals rely on olfaction to find food, attract mates and avoid predators. To support these behaviors, animals must reliably identify odors across different odorant concentrations. The neural circuit operations that implement this concentration invariance remain unclear. Here we demonstrate that, despite concentration-dependence in olfactory bulb (OB), representations of odor identity are preserved downstream, in piriform cortex (PCx). The OB cells responding earliest after inhalation drive robust responses in a sparse subset of PCx neurons. Recurrent collateral connections broadcast their activation across PCx, recruiting strong, global feedback inhibition that rapidly suppresses cortical activity for the remainder of the sniff, thereby discounting the impact of slower, concentration-dependent OB inputs. Eliminating recurrent collateral output dramatically amplifies PCx odor responses, renders cortex steeply concentration-dependent, and abolishes concentration-invariant identity decoding.

neuroscience↗