Biology subjects

Gallimore, C. G.

Publications and source records attributed to Gallimore, C. G..

6 recordsLinked to original sources

bioRxiv2026

A Key Regulator of Dendritic Morphology in Supragranular Neocortex Impacts Mismatch Negativity

BackgroundCytoskeletal structure and neuronal function are heavily intertwined, and altered pyramidal neuron morphology (e.g., reduced dendritic arbors) has been consistently identified in the neocortex of individuals with psychiatric disorders. A missense mutation in Kalrn (Kalrn-PT) enhances activation of RhoA, a cytoskeletal regulator, and leads to adolescent-onset dendritic regression in supragranular auditory cortex. To investigate the relationship between this spatiotemporally altered cytoskeletal structure and psychiatric-relevant dysfunction, we examine the functional impacts of this genetic mutation, focusing on mismatch negativity - a common biomarker of altered sensory integration that matures across adolescence. MethodsIn Kalrn-PT and littermate wild-type mice, pyramidal dendritic morphology was assessed across primary visual cortex (V1) layers using Golgi staining (n=172 neurons/26 mice). Local field potentials (LFPs) and neuronal spiking were recorded during a visual oddball sequence (n=25 mice). Deviance detection - the rodent neural analogue of mismatch negativity - was analyzed across V1 layers. ResultsKalrn-PT mice exhibit reductions in V1 dendritic length specific to layer 2/3, mirroring observations in post-mortem samples from people with psychiatric disorders. Deviance detection was reduced in LFPs from Kalrn-PT mice and absent in layer 2/3 neurons, despite typical feature selectivity and firing rates. These deficits were accompanied by reduced functional connectivity between visual and frontal areas. ConclusionsThese results highlight alterations in higher-level sensory cortical integration in Kalrn-PT mice and demonstrate that adolescent-onset, disease-relevant structural and functional phenotypes can be linked by a common upstream effector. Further, these alterations appear restricted to supragranular layers, demonstrating an outsized role for Kalrn, particularly longer isoforms, in superficial neocortex.

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bioRxiv2026

Global context rapidly shapes sensory responses in V1

Context modulates sensory processing in the cerebral cortex by suppressing responses to expected stimuli and enhancing responses to unexpected ones. Recent proposals argue that early sensory areas such as primary visual cortex (V1) are shaped only by local context, including recent stimulus history, whereas modulation by global context, such as learned temporal structure, is present exclusively in higher cortical areas. This view is incompatible with predictive coding theories. To directly dissociate local and global contextual influences, we used a global/local oddball paradigm in which mice viewed five-item sequences. Across conditions, sequence structure was held constant while stimulus identity and predictability were selectively manipulated, allowing the isolation of response modulations due to local deviance, global expectation, and stimulus repetition independently. In the canonical sequence (AAAA-B), B is locally deviant but globally predictable. Using two-photon calcium imaging and LFP recordings in mouse V1, we found that global predictability abolished context modulation: responses to B were equivalent to those evoked by a random sequence control (e.g., CDEAB). This effect emerged rapidly, after only <10 sequence repetitions, demonstrating fast learning of global structure. When the stimulus was globally deviant, either by replacing B with a novel stimulus (AAAA-C) or by presenting B unpredictably in a standard oddball paradigm, V1 exhibited robust response enhancement. These effects required feedback from anterior cingulate area (ACa), establishing a causal role for higher cortical circuits in conveying global predictions to V1. Strikingly, when an additional A replaced B (AAAA-A), responses were strongly suppressed despite global deviance, indicating that stimulus-specific adaptation may constrain the expression of global prediction error signals in early sensory cortex. HighlightsGlobal context rapidly modulates neural responses in V1 Global deviations, but not predictable local deviants, elicit enhanced responses Downstream brain region ACa is necessary for global context modulation in V1 Standard oddball paradigms involve higher-order contextual modulation

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bioRxiv2026

Cortical deviance detection represents a canonical difference signal

Context modulates neural processing of sensory stimuli. Neural responses are suppressed to stimuli that are typical in their context and augmented to stimuli that deviate from their context. The latter has been conceptualized as a "prediction error", which can serve to enhance the salience, direct attention, or support learning about behaviorally relevant events. Predictive coding theories posit that prediction errors act to signal the difference between internal predictions and actual sensory input, yet most paradigms simultaneously alter both predictions and input, so cannot test for a true difference signal. Increased neural responses to deviants could, instead, encode generalized surprise or augmented bottom-up signaling. Here we compare neural responses to auditory stimuli across oddball paradigm variants. We found that responses of putative excitatory neurons in primary auditory cortex (A1) to auditory deviants contain frequency change information and a memory trace of contextual information. Interestingly, in a fixed-deviant oddball paradigm where predictions are altered but deviant input remains constant, neural response patterns encoded standard-to-deviant frequency difference. These results support the interpretation that A1 deviance detection can be interpreted as a sensory prediction error that represents the difference between prediction and sensory input, a corollary of the predictive coding framework.

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bioRxiv2025

Mismatch negativity develops in adolescence and independently of microglia

Higher brain functions and cognition undergo a critical period of development during adolescence, when psychiatric disorders such as schizophrenia typically onset. Understanding how developmental processes during adolescence interact with schizophrenia pathophysiology and risk remains a central goal in psychiatry. Here we show that a well-established biomarker of schizophrenia, mismatch negativity, matures during adolescence in mouse primary visual cortex, along with a strengthening of fronto-visual functional connectivity. Because microglia are implicated in schizophrenia risk and disease states, we further investigated what role microglia may play in the development of mismatch responses under physiological conditions. We found that microglial depletion with PLX5622 in adolescence arrests the development of resting oscillations in frontal areas, but does not affect the development of deviance detection, other signatures of visual context processing, or prefrontal-visual functional connectivity. Our findings suggest (a) a key component of mismatch negativity develops in adolescence, a period of vulnerability to schizophrenia, and (b) the development underlying this component does not require robust microglia activity, clarifying the developmental role of microglia in higher order visual processing.

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bioRxiv2023

Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses

AbstractContext modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1) -- a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence - a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations - and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that while basic adaptation to redundant stimuli was present early (50ms) in layer 4 responses, DD emerged later (150-230ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7Hz) and high-gamma (70-80Hz) oscillations in L2/3 and decreased beta oscillations (26-36hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, while "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.

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bioRxiv2023

A frontosensory circuit for visual context processing is synchronous in the theta/alpha band

Visual processing is strongly influenced by context. Stimuli that deviate from contextual regularities elicit augmented responses in primary visual cortex (V1). These heightened responses, known as "deviance detection," require both inhibition local to V1 and top-down modulation from higher areas of cortex. Here we investigated the spatiotemporal mechanisms by which these circuit elements interact to support deviance detection. Local field potential recordings in mice in anterior cingulate area (ACa) and V1 during a visual oddball paradigm showed that interregional synchrony peaks in the theta/alpha band (6-12 Hz). Two-photon imaging in V1 revealed that mainly pyramidal neurons exhibited deviance detection, while vasointestinal peptide-positive interneurons (VIPs) increased activity and somatostatin-positive interneurons (SSTs) decreased activity (adapted) to redundant stimuli (prior to deviants). Optogenetic drive of ACa-V1 inputs at 6-12 Hz activated V1-VIPs but inhibited V1-SSTs, mirroring the dynamics present during the oddball paradigm. Chemogenetic inhibition of VIP interneurons disrupted ACa-V1 synchrony and deviance detection responses in V1. These results outline spatiotemporal and interneuron-specific mechanisms of top-down modulation that support visual context processing.

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