scholarly journals Presynaptic mitochondria volume and abundance increase during development of a high-fidelity synapse

2019 ◽  
Author(s):  
Connon I. Thomas ◽  
Christian Keine ◽  
Satoko Okayama ◽  
Rachel Satterfield ◽  
Morgan Musgrove ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Adenoviral Vector ◽  
Auditory Brainstem ◽  
Auditory Information ◽  
Developmental Profile ◽  
Calyx Of Held ◽  
Information Encoding ◽  
Firing Rates ◽  
Block Face ◽  
High Firing

AbstractThe calyx of Held, a large glutamatergic presynaptic terminal in the auditory brainstem undergoes developmental changes to support the high action-potential firing rates required for auditory information encoding. In addition, calyx terminals are morphologically diverse which impacts vesicle release properties and synaptic plasticity. Mitochondria influence synaptic plasticity through calcium buffering and are crucial for providing the energy required for synaptic transmission. Therefore, it has been postulated that mitochondrial levels increase during development and contribute to the morphological-functional diversity in the mature calyx. However, the developmental profile of mitochondrial volumes and subsynaptic distribution at the calyx of Held remains unclear. To provide insight on this, we developed a helper-dependent adenoviral vector (HdAd) that expresses the genetically encoded peroxidase marker for mitochondria, mito-APEX2, at the mouse calyx of Held. We developed protocols to detect labeled mitochondria for use with serial block face scanning electron microscopy to carry out semi-automated segmentation of mitochondria, high-throughput whole terminal reconstruction and presynaptic ultrastructure in mice of either sex. Subsequently, we measured mitochondrial volumes and subsynaptic distributions at the immature postnatal day 7 (P7) and the mature (P21) calyx. We found an increase of mitochondria volumes in terminals and axons from P7 to P21 but did not observe differences between stalk and swelling subcompartments in the mature calyx. Based on these findings, we propose that mitochondrial volumes and synaptic localization developmentally increase to support high firing rates required in the initial stages of auditory information processing.Significance StatementElucidating the developmental processes of auditory brainstem presynaptic terminals is critical to understanding auditory information encoding. Additionally, morphological-functional diversity at these terminals is proposed to enhance coding capacity. Mitochondria provide energy for synaptic transmission and can buffer calcium, impacting synaptic plasticity; however, their developmental profile to ultimately support the energetic demands of synapses following the onset of hearing remains unknown. Therefore, we created a helper-dependent adenoviral vector with the mitochondria-targeting peroxidase mito-APEX2 and expressed it at the mouse calyx of Held. Volumetric reconstructions of serial block face electron microscopy data of immature and mature labeled calyces reveal that mitochondrial volumes are increased to support high firing rates upon maturity.

The Auditory Brainstem Implant

2019 ◽  
pp. 758-770
Author(s):  
Robert V. Shannon
Keyword(s):  
Surgical Technique ◽  
Cochlear Nucleus ◽  
Meta Analysis ◽  
Auditory Brainstem ◽  
Auditory Information ◽  
Speech Understanding ◽  
Auditory Neurons ◽  
Auditory Brainstem Implant ◽  
The Brain ◽  
Implanted Device

The auditory brainstem implant (ABI) is a surgically implanted device to electrically stimulate auditory neurons in the cochlear nucleus complex of the brainstem in humans to restore hearing sensations. The ABI is similar in function to a cochlear implant, but overall outcomes are poorer. However, recent applications of the ABI to new patient populations and improvements in surgical technique have led to significant improvements in outcomes. While the ABI provides hearing benefits to patients, the outcomes challenge our understanding of how the brain processes neural patterns of auditory information. The neural pattern of activation produced by an ABI is highly unnatural, yet some patients achieve high levels of speech understanding. Based on a meta-analysis of ABI surgeries and outcomes, a theory is proposed of a specialized sub-system of the cochlear nucleus that is critical for speech understanding.

scholarly journals Confidence-Related Decision Making

2010 ◽  
Vol 104 (1) ◽  
pp. 539-547 ◽  
Author(s):  
Andrea Insabato ◽  
Mario Pannunzi ◽  
Edmund T. Rolls ◽  
Gustavo Deco
Keyword(s):  
Decision Making ◽  
Cognitive Functioning ◽  
Neuronal Activity ◽  
Emergent Property ◽  
Neuronal Responses ◽  
Attractor Network ◽  
Firing Rates ◽  
Integrate And Fire ◽  
The Brain ◽  
High Firing

Neurons have been recorded that reflect in their firing rates the confidence in a decision. Here we show how this could arise as an emergent property in an integrate-and-fire attractor network model of decision making. The attractor network has populations of neurons that respond to each of the possible choices, each biased by the evidence for that choice, and there is competition between the attractor states until one population wins the competition and finishes with high firing that represents the decision. Noise resulting from the random spiking times of individual neurons makes the decision making probabilistic. We also show that a second attractor network can make decisions based on the confidence in the first decision. This system is supported by and accounts for neuronal responses recorded during decision making and makes predictions about the neuronal activity that will be found when a decision is made about whether to stay with a first decision or to abort the trial and start again. The research shows how monitoring can be performed in the brain and this has many implications for understanding cognitive functioning.

Modeling the short-term dynamics of in vivo excitatory spike transmission

2018 ◽  
Author(s):  
Abed Ghanbari ◽  
Naixin Ren ◽  
Christian Keine ◽  
Carl Stoelzel ◽  
Bernhard Englitz ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Large Scale ◽  
Auditory Brainstem ◽  
Postsynaptic Neuron ◽  
Intracellular Recordings ◽  
Short Term ◽  
Functional Connection ◽  
Synaptic Dynamics ◽  
Synaptic Effects

AbstractInformation transmission in neural networks is influenced by both short-term synaptic plasticity (STP) as well as non-synaptic factors, such as after-hyperpolarization currents and changes in excitability. Although these effects have been widely characterized in vitro using intracellular recordings, how they interact in vivo is unclear. Here we develop a statistical model of the short-term dynamics of spike transmission that aims to disentangle the contributions of synaptic and non-synaptic effects based only on observed pre- and postsynaptic spiking. The model includes a dynamic functional connection with short-term plasticity as well as effects due to the recent history of postsynaptic spiking and slow changes in postsynaptic excitability. Using paired spike recordings, we find that the model accurately describes the short-term dynamics of in vivo spike transmission at a diverse set of identified and putative excitatory synapses, including a thalamothalamic connection in mouse, a thalamocortical connection in a female rabbit, and an auditory brainstem synapse in a female gerbil. We illustrate the utility of this modeling approach by showing how the spike transmission patterns captured by the model may be sufficient to account for stimulus-dependent differences in spike transmission in the auditory brainstem (endbulb of Held). Finally, we apply this model to large-scale multi-electrode recordings to illustrate how such an approach has the potential to reveal cell-type specific differences in spike transmission in vivo. Although short-term synaptic plasticity parameters estimated from ongoing pre- and postsynaptic spiking are highly uncertain, our results are partially consistent with previous intracellular observations in these synapses.Significance StatementAlthough synaptic dynamics have been extensively studied and modeled using intracellular recordings of post-synaptic currents and potentials, inferring synaptic effects from extracellular spiking is challenging. Whether or not a synaptic current contributes to postsynaptic spiking depends not only on the amplitude of the current, but also on many other factors, including the activity of other, typically unobserved, synapses, the overall excitability of the postsynaptic neuron, and how recently the postsynaptic neuron has spiked. Here we developed a model that, using only observations of pre- and postsynaptic spiking, aims to describe the dynamics of in vivo spike transmission by modeling both short-term synaptic plasticity and non-synaptic effects. This approach may provide a novel description of fast, structured changes in spike transmission.

scholarly journals Factors Influencing Short-term Synaptic Plasticity in the Avian Cochlear Nucleus Magnocellularis

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25472 ◽  
Author(s):  
Jason Tait Sanchez Quinones ◽  
Quinones Karla ◽  
Otto-Meyer Sebastian
Keyword(s):  
Synaptic Plasticity ◽  
Cochlear Nucleus ◽  
Time Course ◽  
Synaptic Depression ◽  
Auditory Brainstem ◽  
Short Term ◽  
Nucleus Magnocellularis ◽  
Developmental Shift ◽  
Acid Type ◽  
Synaptic Dynamics

Defined as reduced neural responses during high rates of activity, synaptic depression is a form of short-term plasticity important for the temporal filtering of sound. In the avian cochlear nucleus magnocellularis (NM), an auditory brainstem structure, mechanisms regulating short-term synaptic depression include pre-, post-, and extrasynaptic factors. Using varied paired-pulse stimulus intervals, we found that the time course of synaptic depression lasts up to four seconds at late-developing NM synapses. Synaptic depression was largely reliant on exogenous Ca2+-dependent probability of presynaptic neurotransmitter release, and to a lesser extent, on the desensitization of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPA-R). Interestingly, although extrasynaptic glutamate clearance did not play a significant role in regulating synaptic depression, blocking glutamate clearance at early-developing synapses altered synaptic dynamics, changing responses from depression to facilitation. These results suggest a developmental shift in the relative reliance on pre-, post-, and extrasynaptic factors in regulating short-term synaptic plasticity in NM.

scholarly journals Reconciling the STDP and BCM Models of Synaptic Plasticity in a Spiking Recurrent Neural Network

2010 ◽  
Vol 22 (8) ◽  
pp. 2059-2085 ◽  
Author(s):  
Daniel Bush ◽  
Andrew Philippides ◽  
Phil Husbands ◽  
Michael O'Shea
Keyword(s):  
Neural Network ◽  
Synaptic Plasticity ◽  
Recurrent Neural Network ◽  
Hebbian Learning ◽  
Spike Timing ◽  
Synaptic Competition ◽  
Firing Rates ◽  
Plasticity Rule ◽  
Asymmetric Learning

Rate-coded Hebbian learning, as characterized by the BCM formulation, is an established computational model of synaptic plasticity. Recently it has been demonstrated that changes in the strength of synapses in vivo can also depend explicitly on the relative timing of pre- and postsynaptic firing. Computational modeling of this spike-timing-dependent plasticity (STDP) has demonstrated that it can provide inherent stability or competition based on local synaptic variables. However, it has also been demonstrated that these properties rely on synaptic weights being either depressed or unchanged by an increase in mean stochastic firing rates, which directly contradicts empirical data. Several analytical studies have addressed this apparent dichotomy and identified conditions under which distinct and disparate STDP rules can be reconciled with rate-coded Hebbian learning. The aim of this research is to verify, unify, and expand on these previous findings by manipulating each element of a standard computational STDP model in turn. This allows us to identify the conditions under which this plasticity rule can replicate experimental data obtained using both rate and temporal stimulation protocols in a spiking recurrent neural network. Our results describe how the relative scale of mean synaptic weights and their dependence on stochastic pre- or postsynaptic firing rates can be manipulated by adjusting the exact profile of the asymmetric learning window and temporal restrictions on spike pair interactions respectively. These findings imply that previously disparate models of rate-coded autoassociative learning and temporally coded heteroassociative learning, mediated by symmetric and asymmetric connections respectively, can be implemented in a single network using a single plasticity rule. However, we also demonstrate that forms of STDP that can be reconciled with rate-coded Hebbian learning do not generate inherent synaptic competition, and thus some additional mechanism is required to guarantee long-term input-output selectivity.

scholarly journals GABAergic and glycinergic inhibition modulate monaural auditory response properties in the avian superior olivary nucleus

2011 ◽  
Vol 105 (5) ◽  
pp. 2405-2420 ◽  
Author(s):  
W. L. Coleman ◽  
M. J. Fischl ◽  
S. R. Weimann ◽  
R. M. Burger
Keyword(s):  
Phase Locking ◽  
Auditory Brainstem ◽  
Inhibitory Input ◽  
Auditory Information ◽  
Low Frequencies ◽  
Response Properties ◽  
Glycinergic Inhibition ◽  
Olivary Nucleus

The superior olivary nucleus (SON) is the primary source of inhibition in the avian auditory brainstem. While much is known about the role of inhibition at the SON's target nuclei, little is known about how the SON itself processes auditory information or how inhibition modulates these properties. Additionally, the synaptic physiology of inhibitory inputs within the SON has not been described. We investigated these questions using in vivo and in vitro electrophysiological techniques in combination with immunohistochemistry in the chicken, an organism for which the auditory brainstem has otherwise been well characterized. We provide a thorough characterization of monaural response properties in the SON and the influence of inhibitory input in shaping these features. We found that the SON contains a heterogeneous mixture of response patterns to acoustic stimulation and that in most neurons these responses are modulated by both GABAergic and glycinergic inhibitory inputs. Interestingly, many SON neurons tuned to low frequencies have robust phase-locking capability and the precision of this phase locking is enhanced by inhibitory inputs. On the synaptic level, we found that evoked and spontaneous inhibitory postsynaptic currents (IPSCs) within the SON are also mediated by both GABAergic and glycinergic inhibition in all neurons tested. Analysis of spontaneous IPSCs suggests that most SON cells receive a mixture of both purely GABAergic terminals, as well as terminals from which GABA and glycine are coreleased. Evidence for glycinergic signaling within the SON is a novel result that has important implications for understanding inhibitory function in the auditory brainstem.

scholarly journals Current injection and receptor-mediated excitation produce similar maximal firing rates in hypoglossal motoneurons

2016 ◽  
Vol 115 (3) ◽  
pp. 1307-1313 ◽  
Author(s):  
Hilary E. Wakefield ◽  
Ralph F. Fregosi ◽  
Andrew J. Fuglevand
Keyword(s):  
Time Course ◽  
Input Resistance ◽  
Current Injection ◽  
Synaptic Activity ◽  
High Concentration ◽  
Membrane Potential Change ◽  
Firing Rates ◽  
Whole Cell Patch Clamp ◽  
Patch Clamp Electrophysiology ◽  
High Firing

The maximum firing rates of motoneurons (MNs), activated in response to synaptic drive, appear to be much lower than that elicited by current injection. It could be that the decrease in input resistance associated with increased synaptic activity (but not current injection) might blunt overall changes in membrane depolarization and thereby limit spike-frequency output. To test this idea, we recorded, in the same cells, maximal firing responses to current injection and to synaptic activation. We prepared 300 μm medullary slices in neonatal rats that contained hypoglossal MNs and used whole-cell patch-clamp electrophysiology to record their maximum firing rates in response to triangular-ramp current injections and to glutamate receptor-mediated excitation. Brief pressure pulses of high-concentration glutamate led to significant depolarization, high firing rates, and temporary cessation of spiking due to spike inactivation. In the same cells, we applied current clamp protocols that approximated the time course of membrane potential change associated with glutamate application and with peak current levels large enough to cause spike inactivation. Means (SD) of maximum firing rates obtained in response to glutamate application were nearly identical to those obtained in response to ramp current injection [glutamate 47.1 ± 12.0 impulses (imp)/s, current injection 47.5 ± 11.2 imp/s], even though input resistance was 40% less during glutamate application compared with current injection. Therefore, these data suggest that the reduction in input resistance associated with receptor-mediated excitation does not, by itself, limit the maximal firing rate responses in MNs.

scholarly journals Coordinated neuronal ensembles in primary auditory cortical columns

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jermyn Z See ◽  
Craig A Atencio ◽  
Vikaas S Sohal ◽  
Christoph E Schreiner
Keyword(s):  
Information Processing ◽  
Primary Auditory Cortex ◽  
Local Network ◽  
Auditory Information ◽  
Synchronous Activity ◽  
Information Encoding ◽  
Neuronal Ensembles ◽  
Cortical Columns ◽  
Reduction Techniques ◽  
Evoked Activity

The synchronous activity of groups of neurons is increasingly thought to be important in cortical information processing and transmission. However, most studies of processing in the primary auditory cortex (AI) have viewed neurons as independent filters; little is known about how coordinated AI neuronal activity is expressed throughout cortical columns and how it might enhance the processing of auditory information. To address this, we recorded from populations of neurons in AI cortical columns of anesthetized rats and, using dimensionality reduction techniques, identified multiple coordinated neuronal ensembles (cNEs), which are groups of neurons with reliable synchronous activity. We show that cNEs reflect local network configurations with enhanced information encoding properties that cannot be accounted for by stimulus-driven synchronization alone. Furthermore, similar cNEs were identified in both spontaneous and evoked activity, indicating that columnar cNEs are stable functional constructs that may represent principal units of information processing in AI.

scholarly journals Short-term depression and long-term plasticity together tune sensitive range of synaptic plasticity

2019 ◽  
Author(s):  
Nicolas Deperrois ◽  
Michael Graupner
Keyword(s):  
Synaptic Plasticity ◽  
Firing Rate ◽  
Somatosensory Cortex ◽  
Calcium Transients ◽  
Synaptic Efficacy ◽  
Short Term ◽  
Firing Rates ◽  
Short And Long Term ◽  
Activity Dependent

AbstractSynaptic efficacy is subjected to activity-dependent changes on short- and long time scales. While short-term changes decay over minutes, long-term modifications last from hours up to a lifetime and are thought to constitute the basis of learning and memory. Both plasticity mechanisms have been studied extensively but how their interaction shapes synaptic dynamics is little known. To investigate how both short- and long-term plasticity together control the induction of synaptic depression and potentiation, we used numerical simulations and mathematical analysis of a calcium-based model, where pre- and postsynaptic activity induces calcium transients driving synaptic long-term plasticity. We found that the model implementing known synaptic short-term dynamics in the calcium transients can be successfully fitted to long-term plasticity data obtained in visual- and somatosensory cortex. Interestingly, the impact of spike-timing and firing rate changes on plasticity occurs in the prevalent firing rate range, which is different in both cortical areas considered here. Our findings suggest that short- and long-term plasticity are together tuned to adapt plasticity to area-specific activity statistics such as firing rates.Author summarySynaptic long-term plasticity, the long-lasting change in efficacy of connections between neurons, is believed to underlie learning and memory. Synapses furthermore change their efficacy reversibly in an activity-dependent manner on the subsecond time scale, referred to as short-term plasticity. It is not known how both synaptic plasticity mechanisms – long- and short-term – interact during activity epochs. To address this question, we used a biologically-inspired plasticity model in which calcium drives changes in synaptic efficacy. We applied the model to plasticity data from visual- and somatosensory cortex and found that synaptic changes occur in very different firing rate ranges, which correspond to the prevalent firing rates in both structures. Our results suggest that short- and long-term plasticity act in a well concerted fashion.

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