During wakefulness, pyramidal neurons in the intact brain are bombarded by synaptic input that causes tonic depolarization, increased membrane conductance (i.e., shunting), and noisy fluctuations potential; comparison, acute slices typically experience little background input. Such differences operating conditions can compromise extrapolation of vitro data to explain neuronal operation vivo. For instance, have been identified as integrators class 1 according Hodgkin's classification...

The membrane conductance of a pyramidal neuron in vivo is substantially increased by background synaptic input. Increased conductance, or shunting, does not simply reduce neuronal excitability. Recordings from hippocampal neurons using dynamic clamp revealed that adaptation caused complete cessation spiking the high state, whereas repetitive could persist despite low state. This behavior was reproduced phase plane model and explained shunting-induced increase voltage threshold. threshold...

Multiplexing refers to the simultaneous encoding of two or more signals. Neurons have been shown multiplex, but different stimuli require multiplexing strategies. Whereas frequency and amplitude periodic can be encoded by timing rate same spikes, natural scenes, which comprise areas over intensity varies gradually sparse edges where changes abruptly, a strategy. Recording in vivo from neurons primary somatosensory cortex during tactile stimulation, we found that stimulus onset offset (edges)...

Neurons regulate their excitability by adjusting ion channel levels. Degeneracy – achieving equivalent outcomes (excitability) using different solutions (channel combinations) facilitates this regulation enabling a disruptive change in one to be offset compensatory changes other channels. But neurons must coregulate many properties. Pleiotropy the impact of on more than property complicates because that restores its target value often disrupts How then does neuron simultaneously multiple...

Hippocampal CA1 inhibitory interneurones control the excitability and synchronization of pyramidal cells, participate in hippocampal synaptic plasticity. Pairing theta-burst stimulation (TBS) with postsynaptic depolarization, we induced long-term potentiation (LTP) putative single-fibre excitatory currents (EPSCs) stratum oriens/alveus (O/A) mouse slices. LTP induction was absent metabotropic glutamate receptor 1 (mGluR1) knockout mice, correlated presence mGluR1a, required a Ca2+ rise....

Correlated spiking has been widely observed, but its impact on neural coding remains controversial. Correlation arising from comodulation of rates across neurons shown to vary with the firing individual neurons. This translates into rate and correlation being equivalently tuned stimulus; under those conditions, correlated does not provide information beyond that already available neuron rates. Such correlations are irrelevant can reduce efficiency by introducing redundancy. Using simulations...

Synaptic inhibition by GABA(A) receptors requires a transmembrane chloride gradient. Hyperpolarization or shunting results from outward current produced flowing down this gradient, into the cell. Chloride influx necessarily depletes Therefore, mechanisms that replenish gradient (by reducing intracellular concentration, [Cl(-)](i)) are crucial for maintaining efficacy of receptor-mediated inhibition. ClC-2 is an inward-rectifying channel thought to help extrude because inward rectification...

Neuropathic pain remains notoriously difficult to treat despite numerous drug targets. Here, we offer a novel explanation for this intractability. Computer simulations predicted that qualitative changes in primary afferent excitability linked neuropathic arise through switch spike initiation dynamics when molecular pathologies reach tipping point (criticality), and can be reached via several different (degeneracy). We experimentally tested these predictions by pharmacologically blocking...

Neuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in spinal dorsal horn plays key role that processing. Mechanical allodynia - misperception light touch as painful occurs when compromised. Disinhibition due primarily to chloride dysregulation hypofunction potassium-chloride co-transporter KCC2. Here we show, rats, excitatory neurons are disproportionately affected. This not because differentially dysregulated and...

Action potentials (spikes) are regenerated at each node of Ranvier during saltatory transmission along a myelinated axon. The high density voltage-gated sodium channels required by nodes to reliably transmit spikes increases the risk ectopic spike generation in Here we show that spiking is avoided because KV1 prevent from responding slow depolarization; instead, axons respond selectively rapid depolarization implement high-pass filter. To characterize this filter, compared initiation...

Nociceptive sensory neurons convey pain-related signals to the CNS using action potentials. Loss-of-function mutations in voltage-gated sodium channel Na V 1.7 cause insensitivity pain (presumably by reducing nociceptor excitability) but clinical trials seeking treat inhibiting pharmacologically have struggled. This may reflect variable contribution of excitability. Contrary claims that is necessary for nociceptors initiate potentials, we show can achieve similar excitability different...

The cortex encodes a broad range of inputs. This breadth operation requires sensitivity to weak inputs yet non-saturating responses strong If individual pyramidal neurons were have narrow dynamic range, as previously claimed, then staggered all-or-none recruitment those would be necessary for the population achieve range. Contrary this explanation, we show here through clamp experiments in vitro and computer simulations that under noisy conditions exist intact brain due background synaptic...

ABSTRACT Spinal cord stimulation (SCS) reduces chronic pain. Conventional (40-60 Hz) SCS engages spinal inhibitory mechanisms by activating low-threshold mechanoreceptive afferents with axons in the dorsal columns (DCs). But DC typically causes a buzzing sensation (paresthesia) that can be uncomfortable. Kilohertz-frequency (1-10 kHz) produces analgesia without paresthesia and is thought, therefore, not to activate axons, leaving its mechanism unclear. Here we show rats kilohertz-frequency...

Continuation of spiking after a stimulus ends (i.e. persistent spiking) is thought to support working memory. Muscarinic receptor activation enables among synaptically isolated pyramidal neurons in anterior cingulate cortex (ACC), but detailed characterization that lacking and the underlying mechanisms remain unclear. Here, we show rate ACC insensitive intensity number triggers, can be modulated by injected current, resume several seconds hyperpolarization-imposed quiescence. Using...

BackgroundKilohertz-frequency electric field stimulation (kEFS) applied to the spinal cord can reduce chronic pain without causing buzzing sensation (paresthesia) associated with activation of dorsal column fibers. This suggests that high-rate (SCS) has a mode action distinct from conventional, parasthesia-based SCS. A recent study reported kEFS hyperpolarizes neurons, yet this potentially transformative contradicts previous evidence induces depolarization and was based on patch clamp...