Biology subjects

Ammer, J.

Publications and source records attributed to Ammer, J..

5 recordsLinked to original sources

bioRxiv2023

A cranial implant for stabilizing whole-cell patch-clamp recordings in behaving rodents

BackgroundIn vivo patch-clamp recording techniques provide access to the sub- and suprathreshold membrane potential dynamics of individual neurons during behavior. However, maintaining recording stability throughout behavior is a significant challenge, and while methods for head restraint are commonly used to enhance stability, behaviorally related brain movement relative to the skull can severely impact the success rate and duration of whole-cell patch-clamp recordings. New methodWe developed a low-cost, biocompatible, and 3D-printable cranial implant capable of locally stabilizing brain movement, while permitting equivalent access to the brain when compared to a conventional craniotomy. ResultsExperiments in head-restrained behaving mice demonstrate that the cranial implant can reliably reduce the amplitude and speed of brain displacements, significantly improving the success rate of recordings across repeated bouts of motor behavior. Comparison with existing methodsOur solution offers an improvement on currently available strategies for brain stabilization. Due to its small size, the implant can be retrofitted to most in vivo electrophysiology recording setups, providing a low cost, easily implementable solution for increasing intracellular recording stability in vivo. ConclusionsBy facilitating stable whole-cell patch-clamp recordings in vivo, biocompatible 3D printed implants should accelerate the investigation of single neuron computations underlying behavior.

neuroscience↗

bioRxiv2023

Mechanisms of Premotor-Motor Cortex Interactions during Goal Directed Behavior

Deciphering the neural code underlying goal-directed behavior is a long-term mission in neuroscience1,2. Neurons exhibiting preparation and movement-related activity are intermingled in the premotor and motor cortices3,4, thus concealing the neural code of planned movements. We employed a combination of electrophysiology, pathway-specific optogenetics, phototagging, and inverse reinforcement learning (RL) to elucidate the role of defined neuronal subpopulations in the rat rostral and caudal forelimb areas (RFA and CFA), which correspond to the premotor and motor cortical areas. The inverse RL enabled the functional dissection of spatially intermingled neuronal subpopulations, complementing our pathway-specific optogenetic manipulations and unveiling differential functions of the preparation and movement subpopulations projecting from RFA to CFA. Our results show that the projecting preparation subpopulation suppresses movements, whereas the projecting movement subpopulation promotes actions. We found the influence of RFA on CFA to be adaptable, with the projection either inhibiting or exciting neurons in the superficial and deep CFA layers, depending on context and task phase. These complex interactions between RFA and CFA likely involve the differential recruitment of inhibitory interneurons in the CFA, which is supported by our electron microscopy analysis of the connectivity between these regions. We provide here unprecedented mechanistic insights into how the premotor and primary motor cortices are functionally and structurally interlinked with the potential to advance neuroprosthetics. Graphical abstractThis study provides mechanistic insights into the interactions between the rostral forelimb area (RFA) and the caudal forelimb area (CFA). Specifically, we provide evidence for a differential impact of RFA on CFA depending on the task phase and the targeted CFA layers. RFA contains at least two spatially intermingled subpopulations - one related to movement preparation and one to movement execution. Both subpopulations project to CFA. Here we investigated the impact of these two subpopulations on the activity of the local CFA circuit as well as on the behavior in different contexts. When rats were not involved in a task, the effect of RFA was mainly excitatory in the deep CFA layers, while the superficial layers remained unaffected. This can be interpreted as a non-selective activation of the deep CFA neurons enabling a variety of spontaneous movements. During the preparation phase before a movement, the RFA had an opposite impact on the superficial and deep layers: while the superficial CFA layers were excited by RFA input, the deeper layers were mostly inhibited, minimizing movements and enabling continued holding of a lever. During the movement phase, the inhibitory effect on neurons in the deep CFA layers was counterbalanced by excitation, thus enabling a selected conduction of movements. The opposing effects during preparation and movement phase on CFA deep layers were correlated with increased firing rates of the RFA preparation and movement subpopulations, respectively, making it likely that the inhibition resulted from increased activities of these subpopulation specifically. With an electron microcopy approach we demonstrate that inhibitory and excitatory CFA neurons are directly targeted by RFA, thus providing a mechanism for the bidirectional control of CFA activity. Please note that the depicted impact of RFA on excitatory or inhibitory CFA neurons refers to net effects in this figure, not to the targeting of individual neurons. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/524944v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@4de2d5org.highwire.dtl.DTLVardef@167164forg.highwire.dtl.DTLVardef@e9d298org.highwire.dtl.DTLVardef@101320b_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Dense movement with embedded sparse action-type representations in the output layer of motor cortex

Motor cortex generates descending output necessary for executing a wide range of limb movements. Although movement-related activity has been described throughout motor cortex, the spatiotemporal organization of movement-specific signaling in deep layers remains largely unknown. Here, we recorded layer 5B population dynamics in the caudal forelimb area of motor cortex while mice performed a forelimb push/pull task and found that most neurons show movement-invariant responses, with a minority displaying movement specificity. Cell-type-specific imaging identified that movement-invariant responses dominated pyramidal tract (PT) neuron activity, with a small subpopulation representing movement type, whereas a larger proportion of intratelencephalic (IT) neurons displayed movement-specific signaling. The proportion of IT neurons decoding movement-type peaked prior to movement initiation, while for PT neurons this occurred during movement execution. Our data suggest that layer 5B population dynamics largely reflect movement-invariant signaling, with information related to movement-type being differentially routed through relatively small, distributed subpopulations of projection neurons.

neuroscience↗

bioRxiv2019

Cerebellar-recipient motor thalamus drives behavioral context-specific movement initiation

To initiate goal-directed behavior, animals must transform sensory cues into motor commands that generate appropriately timed actions. Sensorimotor transformations along the cerebellar-thalamocortical pathway are thought to shape motor cortical output and movement timing, but whether this pathway initiates goal-directed movement remains poorly understood. Here, we recorded and perturbed activity in cerebellar-recipient regions of motor thalamus (dentate / interpositus nucleus-recipient regions, MThDN/IPN) and primary motor cortex (M1) in mice trained to execute a cued forelimb lever push task for reward. MThDN/IPN population responses were dominated by a time-locked increase in activity immediately prior to movement that was temporally uncoupled from cue presentation, providing a fixed latency feedforward motor timing signal to M1FL. Blocking MThDN/IPN output suppressed cued movement initiation. Stimulating the MThDN/IPN thalamocortical pathway in the absence of the cue recapitulated cue-evoked M1 membrane potential dynamics and forelimb behavior in the learned behavioral context, but generated semi-random movements in an altered behavioral context. Thus, cerebellar-recipient motor thalamocortical input to M1 is indispensable for the generation of motor commands that initiate goal-directed movement, refining our understanding of how the cerebellar-thalamocortical pathway contributes to movement timing.

neuroscience↗

bioRxiv2017

GABA regulates resonance and spike rate encoding via a universal mechanism that underlies the modulation of action potential generation

Different mechanisms for action potential (AP) generation exist that shape neuronal coding and network dynamics. The neuro-transmitter GABA regulates neuronal activity but its role in modulating AP dynamics itself is unclear. Here we show that GABA indeed changes the AP mechanism: it causes regularly firing hippocampal CA3 neurons to bistably switch between spiking and quiescence, converts graded discharge-to-current relationships to have abrupt onsets, and induces resonance. Modeling reveals that A-currents enable these GABA-induced transitions. Mathematically, we prove that this transition sequence originates from a single universal principle that generically underlies the modulation of AP dynamics in any conductance-based neuron model. Conductance clamp experiments in hippocampal and brainstem neurons show the same transitions, confirming the universal theory. In simulated networks, synaptically controlled AP dynamics, permits dynamic gating of signals and targeted synchronization of neuronal sub-ensembles. These results advance the systematic understanding of AP modulation and its role in neuronal and network function.

neuroscience↗