Biology subjects

Ellender, T. J.

Publications and source records attributed to Ellender, T. J..

8 recordsLinked to original sources

bioRxiv2026

The Effect of Neurodegeneration on Ultrasonic Vocalisations (USV) and Their Neuronal Substrates in Mice and Rats: A Systematic Review

This systematic review examines the effects of neurodegeneration in rats and mice on ultrasonic vocalisation (USV) production and its underlying neuronal substrates. Neurodegenerative diseases, such as Parkinsons, Alzheimers, and frontotemporal degeneration, significantly impair communication abilities in humans. Animal models, particularly rats and mice, are widely used to study the underlying mechanisms of these disorders. One important aspect of neurodegeneration is its impact on ultrasonic vocalisations in rodents. USVs play a crucial role in social interaction, mating, and distress signalling, making them valuable behavioural biomarkers for neurological dysfunction. This review aims to synthesise existing research on how neurodegeneration affects USV production and its neuronal substrates in rodent models. Understanding these changes can provide insights into disease progression and facilitate the development of early diagnostic tools and therapeutic strategies. Studying USV impairments in animal models may help identify biomarkers relevant to human speech deficits in neurodegenerative diseases. By bridging the gap between preclinical and clinical research, this review contributes to the growing field of neurobehavioral biomarkers, which could ultimately improve early diagnosis and intervention in human neurodegenerative conditions.

neuroscience↗

bioRxiv2025

Modulation of hippocampal synaptic transmission by mast cells at the hippocampal-thalamic border during early brain development

Synaptic development is a highly structured process and can be modulated by the biogenic amine, histamine, whose dysregulation during brain development can be part of the aetiology of the neurodevelopmental disorders Tourettes syndrome and OCD. Well documented in the literature is the extensive histaminergic axonal innervation originating from neurons in tuberomammillary nucleus of the hypothalamus, however, less is known about non-neuronal sources of histamine, such as mast cells, and their potential functional importance in development. Here we set out to investigate the spatiotemporal localisation of mast cells in the developing C57Bl/6 mouse brain and the potential impact of their degranulation on developing synapses. Firstly, we find that the mouse brain contains relatively larger numbers of mast cells during the first and second postnatal week. Secondly, that in this period the highest density of mast cells is found just below the hippocampus at the hippocampal-thalamic border with lower numbers found in other brain regions. Thirdly, using the mast cell degranulator C48/80 we observe that their degranulation can facilitate synaptic transmission at the perforant pathway inputs to the ventral portion of the dentate gyrus which could not be blocked by co-application of the histamine H3 receptor antagonist thioperamide. In contrast histamine superfusion tended to decrease synaptic transmission at this pathway which was sensitive to thioperamide co-application. In conclusion, these results suggest that mast cells are present in the developing C57Bl/6 mouse brain and in particular at the hippocampal-thalamic border where upon degranulation they appear to modulate hippocampal synaptic transmission.

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bioRxiv2023

Histamine originating from the BNST modulates corticostriatal synaptic transmission during early postnatal development

The neuromodulator histamine regulates key processes in many regions of both the adult and developing brain including the striatum. However, striatal innervation by histaminergic afferents is very sparse making the physiological sources of histamine controversial. Here potential sources of striatal histamine were investigated during early postnatal development and specifically in the second postnatal week, in acute mouse brain slices. Firstly, a combination of whole-cell patch-clamp recordings and optogenetic stimulation demonstrates that during this period exogenously applied histamine modulates the intrinsic properties of developing D1 and D2 striatal spiny projection neurons (SPNs) as well as synaptic transmission at afferents coming from the mPFC and visual cortex. Secondly, immunohistochemistry for histamine reveals a brain region proximal and caudal to striatum densely innervated by histaminergic axons and corresponding to the oval nucleus of the bed nucleus of stria terminalis (ovBNST). Thirdly, direct electrical stimulation of the ovBNST leads to significant and detectable levels of histamine in the striatum, as assessed by both fast scan cyclic voltammetry and fluorescent histamine sensors. Lastly, electrical stimulation of the ovBNST nucleus, at frequencies mimicking active histaminergic neurons, can release sufficient levels of histamine to modulate excitatory synaptic transmission from mPFC onto striatal SPNs by acting at histamine H3 receptors. Together, these results provide evidence for the existence of the ovBNST as an extrastriatal source of histamine during early brain development and postulates a new view of the modus operandi of histamine in that it can cross anatomical boundaries and act as a paracrine neuromodulator. Significance statementHistamine is synthesized by neurons in the hypothalamic tuberomammillary nucleus (TMN) and released from their axons in many brain regions controlling key physiological processes. When dysregulated this can result in neurological and neurodevelopmental disorders such as Tourettes syndrome and OCD. To understand the physiological roles for histamine and to facilitate the generation of new therapeutic interventions it is key to define the sources of histamine and its mode of action. Here we provide evidence, using the developing striatum as an exemplar, that sources of histamine can lie beyond anatomical boundaries with histamine acting as a paracrine neuromodulator. This also has potential implications for our mechanistic understanding of deep brain stimulation of the BNST in treating severe Tourettes syndrome and OCD.

neuroscience↗

bioRxiv2022

Generation and propagation of network bursts in the basal ganglia exhibit dynamic changes during early postnatal development

The neonatal brain is characterised by intermittent bursts of oscillatory activity interspersed by relative silence. While these bursts of activity are well characterised for many cortical areas much less is known whether and how these propagate and interact with subcortical regions. Here, early network activity was recorded using silicon probes from the developing basal ganglia, including the motor/somatosensory cortex, dorsal striatum and intralaminar thalamus, during the first two postnatal weeks in mice. Using an unsupervised detection and classification method, two main classes of bursting activity were found, consisting of spindle bursts (SB) and nested gamma spindle bursts (NGB), which were characterised by oscillatory activity at respectively [~]10 Hz and [~]30 Hz. These bursts were reliably identified across all three brain structures but differed in their structural, spectral, and developmental characteristics. Coherence and cross-correlation analyses revealed that burst events often occur synchronously across different brain regions and were mostly of a similar type, especially between cortex and striatum, which also exhibited the strongest interactions as compared to other brain regions. Interestingly, the preferred frequency for these interactions suggested a developmental shift from initial lower frequencies to higher frequencies across development. Together, these results provide the first detailed description of early network activity within the developing basal ganglia and suggests that distinct brain regions drive and coordinate burst activity at different developmental stages.

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bioRxiv2022

Cortical integration of higher-order thalamic inputs is lineage-dependent

Primary sensory cortex receives and integrates inputs from first-order and higher-order thalamic nuclei. First-order inputs convey sensory information from the periphery and exhibit simple response properties, whereas higher-order inputs exhibit more complex response properties, provide contextual feedback, and can modulate first-order inputs. Here we show that the way in which cortical neurons integrate these thalamic inputs, reflects the progenitor cell from which the cortical neurons derive. Within layer 4 of mouse primary somatosensory cortex, excitatory neurons that derive from apical intermediate progenitors exhibit multi-whisker response properties and receive higher-order thalamic input, in a manner consistent with their dendritic morphology. These properties depend upon the expression levels of the transcription factor Lhx2, which when increased, abolishes the higher-order properties of apical intermediate progenitor-derived neurons, and disrupts the induction of sensory-evoked plasticity. These data reveal a lineage-dependent mechanism that establishes the integration and functional contribution of higher-order thalamic inputs within cortex.

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bioRxiv2019

Distinct neural progenitor pools in the ventral telencephalon generate diversity in striatal spiny projection neurons

Heterogeneous populations of neural progenitors in the embryonic lateral ganglionic eminence (LGE) generate all GABAergic spiny projection neurons (SPNs) found in the striatum. Here we investigate how this diversity in neural progenitors relates to diversity of adult striatal neurons and circuits. Using a combination of in utero electroporation to fluorescently pulse-label striatal neural progenitors in the LGE, brain slice electrophysiology, electrical and optogenetic circuit mapping and immunohistochemistry, we characterise a population of neural progenitors enriched for apical intermediate progenitors (aIPs) and a distinct population of other progenitors (OPs) and their neural offspring. We find that neural progenitor origin has subtle but significant effects on the properties of striatal SPNs. Although aIP and OP progenitors can both generate D1-expressing direct pathway as well as D2-expressing indirect pathway SPNs found intermingled in the striatum, the aIP derived SPNs are found in more medial aspects of the striatum, exhibit more complex dendritic arbors with higher spine density and differentially sample cortical input. Moreover, optogenetic circuit mapping of the aIP derived neurons show that they further integrate within striatal circuits and innervate both local D1 and D2 SPNs. These results show that it is possible to fluorescently pulse-label distinct neural progenitor pools within the LGE and provide the first evidence that neural progenitor heterogeneity can contribute to the diversity of striatal SPNs.

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bioRxiv2018

Early postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons

A dysfunctional striatum is thought to contribute to neurodevelopmental disorders such as ADHD, Tourettes syndrome and OCD. Insight into these disorders is reliant on an understanding of the normal development of the striatal cellular and circuit properties. Here we combined whole-cell patch-clamp electrophysiology and anatomical reconstructions of D1 and D2 striatal projection neurons (SPNs) in brain slices to characterize the development of the electrophysiological and morphological properties as well as their long-range and local inputs during the first three postnatal weeks. Overall, we find that many properties develop in parallel but we make several key observations. Firstly, that the electrophysiological properties of young D1 SPNs are more mature and that distinctions between D1 and D2 SPNs become apparent in the second postnatal week. Secondly, that dendrites and spines as well as excitatory inputs from cortex develop in parallel with cortical inputs exhibiting a prolonged period of maturation involving changes in postsynaptic glutamate receptors. Lastly, that initial local connections between striatal SPNs consist of gap junctions, which are gradually replaced by inhibitory synaptic connections. Interestingly, relative biases in inhibitory synaptic connectivity seen between SPNs in adulthood, such as a high connectivity between D2 SPNs, are already evident in the second postnatal week. Combined, these results provide an experimental framework for future investigations of striatal neurodevelopmental disorders and show that many of the cellular and circuit properties are established in the first and second postnatal weeks suggesting intrinsic programs guide their development.\n\nSignificance StatementNormal brain development involves the formation of neurons, which develop correct electrical and morphological properties and are precisely connected with each other in a neural circuit. In neurodevelopmental disorders these processes go awry leading to behavioral and cognitive problems later in life. Here we provide for the first time a detailed quantitative description of the cellular and circuit properties of the two main neuron types of the striatum during the first postnatal weeks. This can form an experimental framework for future studies into neurodevelopmental disorders. We find that most of the properties for both types of striatal neuron develop in parallel and are already established by the second postnatal week suggesting a key role for intrinsic programs in guiding their development.

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bioRxiv2018

Fine-scale excitatory cortical circuits reflect embryonic progenitor pools

Introductory paragraph Introductory paragraph Main text Animals In utero electroporation Intrathalamic injections Slice preparation and recording... Stimulation and recording... Analysis of recordings Histological analyses Statistics Methods Author Contributions References The mammalian neocortex is characterised by precise patterns of synaptic connections, which dictate how information flows through cortical circuits. The degree of convergence and divergence of excitatory information results from highly non-random, short-range and long-range glutamatergic synaptic connections1-11. Previous seminal work has shown that c ...

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