The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

Mowery, Todd M.; Penikis, Kristina B.; Young, Stephen K.; Ferrer, Christopher E.; Kotak, Vibhakar C.; Sanes, Dan H.

doi:10.1016/j.celrep.2017.05.083

Cited by 23 publications

(41 citation statements)

References 29 publications

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“…Interestingly, the relative biases in connectivity (e.g. the high connectivity probability between D2 SPNs) seen in adulthood in this study and by others (Planert et al, 2010) are already established in the second postnatal week prior to when sensory inputs from afferent structures is thought to have arrived (Tobach et al, 1971;Ko et al, 2013;Mowery et al, 2015;Mowery et al, 2017).…”

Section: Local Connections Between D1 and D2 Spnssupporting

confidence: 52%

“…In conclusion we find that the intrinsic cellular and circuit properties of the D1expressing direct pathway and the D2-expressing indirect pathway SPNs exhibit many developmental similarities. Nonetheless, mature D1 and D2 SPNs exhibit distinct electrical properties and form precise local inhibitory connections, which we show are already apparent in the second postnatal week before sensory input from afferent structures is thought to have arrived (Tobach et al, 1971;Ko et al, 2013;Mowery et al, 2015;Mowery et al, 2017). This leaves scope for factors such as intrinsic genetic programs (Arlotta et al, 2008), spontaneous early network patterns (Khazipov et al, 2004;Hanganu-Opatz, 2010;Dehorter et al, 2011;Ackman et al, 2012) and neuromodulators (Kozorovitskiy et al, 2015;Lieberman et al, 2018) in shaping the development of the D1 and D2 SPNs and might inform future investigations of striatal formation in neurodevelopmental disorders (Graybiel & Rauch, 2000;Del Campo et al, 2011;Langen et al, 2011;McNaught & Mink, 2011;Shepherd, 2013;Albin, 2018).…”

Section: Local Connections Between D1 and D2 Spnsmentioning

confidence: 65%

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

Krajeski

Macey-Dare

Heusden

et al. 2018

Preprint

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A dysfunctional striatum is thought to contribute to neurodevelopmental disorders such as ADHD, Tourette's 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. Significance 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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Section: Local Connections Between D1 and D2 Spnssupporting

confidence: 52%

Section: Local Connections Between D1 and D2 Spnsmentioning

confidence: 65%

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

Krajeski

Macey-Dare

Heusden

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…In conclusion, we show that early postnatal development of the intrinsic cellular and circuit properties of the D1-expressing direct pathway and the D2-expressing indirect pathway SPNs is highly dynamic but follows a clear developmental trajectory. Moreover, we show that many of the properties of mature D1 and D2 SPNs are already apparent by the first and second postnatal weeks, which is thought to be a period prior to much exploratory motor behaviour (Dehorter et al 2011) or exposure to structured input from the sensory periphery (Tobach et al 1971;Krug et al 2001;Akerman et al 2002;Ko et al 2013;Mowery et al 2015Mowery et al , 2016Mowery et al , 2017. This is consistent with the idea that neuronal specification can occur early in development (Lobo et al 2006(Lobo et al , 2008Arlotta et al 2008;Ehrman et al 2013;Lu et al 2014;Zhang et al 2016;Merchan-Sala et al 2017;Kelly et al 2018;Tinterri et al 2018;Xu et al 2018) with further postnatal development guided by, for example, neural activity (Zhang & Poo, 2001;Kozorovitskiy et al 2012;Peixoto et al 2016) and neuromodulation (Kozorovitskiy et al 2015;Lieberman et al 2018).…”

Section: Local Inhibitory Synaptic Connections Between D1 and D2 Spnsmentioning

confidence: 75%

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

Krajeski

Macey-Dare

Heusden

et al. 2019

The Journal of Physiology

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Key points Imbalances in the activity of the D1‐expressing direct pathway and D2‐expressing indirect pathway striatal projection neurons (SPNs) are thought to contribute to many basal ganglia disorders, including early‐onset neurodevelopmental disorders such as obsessive–compulsive disorder, attention deficit hyperactivity disorder and Tourette's syndrome. This study provides the first detailed quantitative investigation of development of D1 and D2 SPNs, including their cellular properties and connectivity within neural circuits, during the first postnatal weeks. This period is highly dynamic with many properties changing, but it is possible to make three main observations: many aspects of D1 and D2 SPNs progressively mature in parallel; there are notable exceptions when they diverge; and many of the defining properties of mature striatal SPNs and circuits are already established by the first and second postnatal weeks, suggesting guidance through intrinsic developmental programmes. These findings provide an experimental framework for future studies of striatal development in both health and disease. Abstract Many basal ganglia neurodevelopmental disorders are thought to result from imbalances in the activity of the D1‐expressing direct pathway and D2‐expressing indirect pathway striatal projection neurons (SPNs). Insight into these disorders is reliant on our understanding of normal D1 and D2 SPN development. Here we provide the first detailed study and quantification of the striatal cellular and circuit changes occurring for both D1 and D2 SPNs in the first postnatal weeks using in vitro whole‐cell patch‐clamp electrophysiology. Characterization of their intrinsic electrophysiological and morphological properties, the excitatory long‐range inputs coming from cortex and thalamus, as well their local gap junction and inhibitory synaptic connections reveals this period to be highly dynamic with numerous properties changing. However it is possible to make three main observations. Firstly, many aspects of SPNs mature in parallel, including intrinsic membrane properties, increases in dendritic arbours and spine densities, general synaptic inputs and expression of specific glutamate receptors. Secondly, there are notable exceptions, including a transient stronger thalamic innervation of D2 SPNs and stronger cortical NMDA receptor‐mediated inputs to D1 SPNs, both in the second postnatal week. Thirdly, many of the defining properties of mature D1 and D2 SPNs and striatal circuits are already established by the first and second postnatal weeks, including different electrophysiological properties as well as biased local inhibitory connections between SPNs, suggesting this is guided through intrinsic developmental programmes. Together these findings provide an experimental framework for future studies of D1 and D2 SPN development in health and disease.

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“…We evaluated the relationship between weakened cortical inhibition and auditory perceptual deficits following developmental HL in juvenile gerbils reared with bilateral earplugs. Developmental HL impairs ACx synaptic inhibition, and also degrades an associated perceptual skill, amplitude modulation (AM) detection (Caras and Sanes, 2015;Mowery et al, 2015Mowery et al, , 2017. Here, we report that HL also reduced inhibition in auditory thalamus, the ventral nucleus of the medial geniculate body (MGv).…”

Section: Introductionmentioning

confidence: 87%

Preserving Inhibition during Developmental Hearing Loss Rescues Auditory Learning and Perception

Mowery¹,

Caras²,

Hassan³

et al. 2019

J. Neurosci.

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Transient periods of childhood hearing loss can induce deficits in aural communication that persist long after auditory thresholds have returned to normal, reflecting long-lasting impairments to the auditory CNS. Here, we asked whether these behavioral deficits could be reversed by treating one of the central impairments: reduction of inhibitory strength. Male and female gerbils received bilateral earplugs to induce a mild, reversible hearing loss during the critical period of auditory cortex development. After earplug removal and the return of normal auditory thresholds, we trained and tested animals on an amplitude modulation detection task. Transient developmental hearing loss induced both learning and perceptual deficits, which were entirely corrected by treatment with a selective GABA reuptake inhibitor (SGRI). To explore the mechanistic basis for these behavioral findings, we recorded the amplitudes of GABA A and GABA B receptor-mediated IPSPs in auditory cortical and thalamic brain slices. In hearing loss-reared animals, cortical IPSP amplitudes were significantly reduced within a few days of hearing loss onset, and this reduction persisted into adulthood. SGRI treatment during the critical period prevented the hearing loss-induced reduction of IPSP amplitudes; but when administered after the critical period, it only restored GABA B receptor-mediated IPSP amplitudes. These effects were driven, in part, by the ability of SGRI to upregulate ␣1 subunitdependent GABA A responses. Similarly, SGRI prevented the hearing loss-induced reduction of GABA A and GABA B IPSPs in the ventral nucleus of the medial geniculate body. Thus, by maintaining, or subsequently rescuing, GABAergic transmission in the central auditory thalamocortical pathway, some perceptual and cognitive deficits induced by developmental hearing loss can be prevented.

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The Sensory Striatum Is Permanently Impaired by Transient Developmental Deprivation

Cited by 23 publications

References 29 publications

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

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

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

Preserving Inhibition during Developmental Hearing Loss Rescues Auditory Learning and Perception

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