Biology subjects

Kohl, M. M.

Publications and source records attributed to Kohl, M. M..

6 recordsLinked to original sources

bioRxiv2023

Memory encoding and retrieval by retrosplenial parvalbumin interneurons is impaired in Alzheimer's disease model mice

Memory deficits in Alzheimers disease (AD) show a strong link with GABAergic interneuron dysfunctions1-7. Ensemble dynamics of GABAergic interneurons are critical in memory encoding and retrieval8-12 but how GABAergic interneuron dysfunction affects inhibitory ensemble dynamics in AD is unknown. As retrosplenial cortex (RSC) is a brain area critical for episodic memory13-16 and affected by beta-amyloid accumulation in early AD17-21, we address this question by performing Ca2+ imaging in RSC parvalbumin-expressing (PV) interneurons during a contextual fear memory (CFM) task in healthy control mice and the 5XFAD mouse model of AD. We found that subpopulations of PV interneurons that were responsive to aversive electric foot shocks during contextual fear conditioning (CFC) in the control mice significantly decreased in the 5XFAD mice, indicating a dysfunction in the recruitment of CFM-encoding PV interneurons. In control mice, CFC-responsive PV interneuron ensemble activities were selectively upregulated during the freezing epoch of the CFM retrieval, manifested by CFC-induced synaptic potentiation of PV interneuron-mediated inhibition. However, CFC-induced changes in PV interneuron ensemble dynamics during CFM retrieval and synaptic plasticity were both absent in the 5XFAD mice. Optogenetic silencing of PV interneurons during CFC in control mice mimicked the CFM deficits in 5XFAD mice, while optogenetic activation of PV interneurons during CFC in the 5XFAD mice restored CFM retrieval. These results demonstrate the necessity and sufficiency of CFC-responsive PV interneurons for CFM retrieval and suggest that synaptic dysfunction in CFM-encoding PV interneurons disrupt the inhibitory ensemble dynamics underlying CFM retrieval, subsequently leading to memory deficits in AD.

neuroscience↗

bioRxiv2022

Stimulus information guides the emergence of behavior related signals in primary somatosensory cortex during learning

Cortical neurons in primary sensory cortex carry not only sensory but also behavior-related information. However, it remains unclear how these types of information emerge and are integrated with one another over learning and what the relative contribution of activity in individual cells versus neuronal populations is in this process. Current evidence supports two opposing views of learning-related changes: 1) sensory information increases in primary cortex or 2) sensory information remains stable in primary cortex but its readout efficiency in association cortices increases. Here, we investigate these questions in primary sensory cortex during learning of a sensory task. Over the course of weeks, we imaged neuronal activity at different depths within layers 2 and 3 of the mouse vibrissal primary somatosensory cortex (vS1) before, during, and after training on a whisker-based object-localization task. We leveraged information theoretical analysis to quantify stimulus and behavior-related information in vS1 and estimate how much neural activity encoding sensory information is used to inform perceptual choices as sensory learning progresses. We also quantified the extent to which these types of information are supported by an individual neuron or population code. We found that, while sensory information rises progressively from the start of training, choice information is only present in the final stages of learning and is increasingly supported by a population code. Moreover, we demonstrate that not only the increase in available information, but also a more efficient readout of such information in primary sensory cortex mediate sensory learning. Together, our results highlight the importance of primary cortical neurons in perceptual learning.

neuroscience↗

bioRxiv2021

Retrosplenial cortex is necessary for spatial and non-spatial latent learning in mice

Latent learning occurs when associations are formed between stimuli in the absence of explicit reinforcement. Traditionally, latent learning in rodents has been associated with the creation internal models of space. However, increasing evidence points to roles of internal models also in non-spatial decision making. Whether the same brain structures and processes support the creation of spatially-anchored or non-spatial internal models via latent learning, is an open question. To address this question, we developed a novel operant box task that allows to test spatial and non-spatial versions of a flavour-based sensory preconditioning paradigm. We probed the role of the retrosplenial cortex, a brain area associated with spatial cognition and subjective value representation, in this task using precise, closed-loop optogenetic silencing during different task phases. We show that the retrosplenial cortex is necessary for both spatial and non-spatial latent learning in mice. We further demonstrate that the requirement of retrosplenial cortex is limited to the preconditioning phase of the task. Our results provide insight into the specific role of the retrosplenial cortex in latent learning, demonstrate that latent learning plays a general part in the creation of internal models, independent of spatial anchors, and provide a novel avenue for studying model-based decision making.

neuroscience↗

bioRxiv2021

Contribution of interneuron subtype-specific GABAergic signalling to emergent sensory processing in somatosensory whisker barrel cortex in mouse.

Mammalian neocortex is important for conscious processing of sensory information. Fundamental to this function is balanced glutamatergic and GABAergic signalling. Yet little is known about how this interaction arises in the developing forebrain despite increasing insight into early GABAergic interneuron (IN) circuits. To further study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex. Specifically we explored the role of INs in speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity, and showed refinement over the period leading to active whisking onset. We then conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked activity in an age and layer-dependent manner. Silencing SST+ INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP+ IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results reveal how these IN subtypes differentially contribute to early sensory processing over the first few postnatal weeks.

neuroscience↗

bioRxiv2019

Neocortical inhibitory interneuron subtypes display distinct responses to synchrony and rate of inputs

Populations of neurons in the neocortex can carry information with both the synchrony and the rate of their spikes. However, it is unknown whether distinct subtypes of neurons in the cortical microcircuit are more sensitive to information carried by synchrony versus rate. Here, we address this question using patterned optical stimulation in slices of barrel cortex from transgenic mouse lines labelling distinct interneuron populations: fast-spiking parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons. We use optical stimulation of channelrhodopsin-2 (ChR2) expressing excitatory neurons in layer 2/3 in order to encode a random 1-bit signal in either the synchrony or rate of activity in presynaptic cells. We then examine the mutual information between this 1-bit signal and the voltage and spiking responses in PV+ and SST+ interneurons. Generally, we find that both interneuron types carry more information than GFP negative (GFP-) control cells. More specifically, we find that for a synchrony encoding, PV+ interneurons carry more information in the first 5 milliseconds, while both interneuron subtypes carry more information than negative controls in their later response. We also find that for a rate encoding, SST+ interneurons carry more information than either PV+ or negative controls after several milliseconds. These data demonstrate that inhibitory interneuron subtypes in the neocortex have distinct responses to information carried by synchrony versus rates of spiking.

neuroscience↗

bioRxiv2018

Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomers in vivo

Abnormal accumulation of amyloid {beta} oligomers (A{beta}O) is a hallmark of Alzheimers disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether A{beta}O selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with A{beta}O pathology in vivo, we co-injected A{beta}O and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordings in vivo in these A{beta}O-injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in A{beta}O-injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice. In vitro whole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with A{beta}O revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in A{beta}O-injected mice in vivo. Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.

neuroscience↗