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Nelson Spruston

Publications and source records attributed to Nelson Spruston.

10 recordsLinked to original sources
PubMed2005

Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites.

We performed simultaneous patch-electrode recordings from the soma and apical dendrite of CA1 pyramidal neurons in hippocampal slices, in order to determine the degree of voltage attenuation along CA1 dendrites. Fifty per cent attenuation of steady-state somatic voltage changes occurred at a distance of 238 microm from the soma in control and 409 microm after blocking the hyperpolarization-activated (H) conductance. The morphology of three neurons was reconstructed and used to generate computer models, which were adjusted to fit the somatic and dendritic voltage responses. These models identify several factors contributing to the voltage attenuation along CA1 dendrites, including high axial cytoplasmic resistivity, low membrane resistivity, and large H conductance. In most cells the resting membrane conductances, including the H conductances, were larger in the dendrites than the soma. Simulations suggest that synaptic potentials attenuate enormously as they propagate from the dendrite to the soma, with greater than 100-fold attenuation for synapses on many small, distal dendrites. A prediction of this powerful EPSP attenuation is that distal synaptic inputs are likely only to be effective in the presence of conductance scaling, dendritic excitability, or both.

Animals↗
PubMed2005

R-type calcium channels contribute to afterdepolarization and bursting in hippocampal CA1 pyramidal neurons.

Action potentials in pyramidal neurons are typically followed by an afterdepolarization (ADP), which in many cells contributes to intrinsic burst firing. Despite the ubiquity of this common excitable property, the responsible ion channels have not been identified. Using current-clamp recordings in hippocampal slices, we find that the ADP in CA1 pyramidal neurons is mediated by an Ni2+-sensitive calcium tail current. Voltage-clamp experiments indicate that the Ni2+-sensitive current has a pharmacological and biophysical profile consistent with R-type calcium channels. These channels are available at the resting potential, are activated by the action potential, and remain open long enough to drive the ADP. Because the ADP correlates directly with burst firing in CA1 neurons, R-type calcium channels are crucial to this important cellular behavior, which is known to encode hippocampal place fields and enhance synaptic plasticity.

Action Potentials↗
PubMed2005

Output-mode transitions are controlled by prolonged inactivation of sodium channels in pyramidal neurons of subiculum.

Transitions between different behavioral states, such as sleep or wakefulness, quiescence or attentiveness, occur in part through transitions from action potential bursting to single spiking. Cortical activity, for example, is determined in large part by the spike output mode from the thalamus, which is controlled by the gating of low-voltage-activated calcium channels. In the subiculum--the major output of the hippocampus--transitions occur from bursting in the delta-frequency band to single spiking in the theta-frequency band. We show here that these transitions are influenced strongly by the inactivation kinetics of voltage-gated sodium channels. Prolonged inactivation of sodium channels is responsible for an activity-dependent switch from bursting to single spiking, constituting a novel mechanism through which network dynamics are controlled by ion channel gating.

Adenosine Diphosphate↗
PubMed2004

Peering into the dendritic machinery of striatal medium spiny neurons.

Striatal medium spiny neurons are principal players in the basal ganglia macrocircuits implicated in an astonishing array of psychomotor disorders, including Parkinson's disease, schizophrenia, Huntington's disease, and drug abuse. Using an elegant combination of 2-photon laser scanning microscopy and 2-photon uncaging of glutamate, Carter and Sabatini (this issue of Neuron) provide our first glimpse into the dendrites and spines of striatal medium spiny neurons. The results offer new insights into the workings of these clinically important yet mysterious neurons.

Action Potentials↗
PubMed2003

Psychostimulant-induced plasticity of intrinsic neuronal excitability in ventral subiculum.

Psychostimulant drugs such as amphetamine are prescribed to increase vigilance, suppress appetite, and treat attention disorders, but they powerfully activate the dopamine system and have serious abuse potential. Repeated psychostimulant exposure induces neuronal plasticity within the mesolimbic dopamine system. Here we present evidence that repeated amphetamine exposure results in a suppression of intrinsic neuronal excitability in the ventral subiculum, a hippocampal region that activates dopamine neurotransmission. We used patch-clamp recordings from brain slices obtained at different times after withdrawal from repeated amphetamine exposure to determine the long-term effects of amphetamine on subicular excitability. Using several postsynaptic indices of sodium channel function, our results show that excitability is decreased for days, but not weeks, after repeated amphetamine exposure. The resulting increase in action potential threshold and decrease in postsynaptic amplification of excitatory synaptic input provide the first direct evidence that psychostimulants induce plasticity of hippocampal output and suggest one mechanism by which drug withdrawal may influence limbic dopamine-dependent learning and memory.

Action Potentials↗
PubMed2003

Intracellular correlate of EPSP-spike potentiation in CA1 pyramidal neurons is controlled by GABAergic modulation.

The hippocampus has been used extensively as a model to study plastic changes in the brain's neural circuitry. Immediately after high-frequency stimulation to hippocampal Schaffer collateral axons, a dramatic change occurs in the relationship between the presynaptic CA3 and the postsynaptic CA1 pyramidal neurons. For a fixed excitatory postsynaptic potential (EPSP), there arises an increased likelihood of action potential generation in the CA1 pyramidal neuron. This phenomenon is called EPSP-spike (E-S) potentiation. We explored E-S potentiation, using patch-clamp techniques in the hippocampal slice preparation. A specific protocol was developed to measure the action potential probability for a given synaptic strength, which allowed us to quantify the amount of E-S potentiation for a single neuron. E-S potentiation was greatest when gamma-aminobutyric acid (GABA)ergic inhibition was intact, suggesting that modulation of inhibition is a major aspect of E-S potentiation. Expression of E-S potentiation also correlated with a reduced action-potential threshold, which was greatest when GABAergic inhibition was intact. Conditioning stimuli produced a smaller threshold reduction when inhibition was blocked, but some reduction also occurred in the absence of a conditioning stimulus. Together, these results suggest that E-S potentiation is caused primarily through a reduction of GABAergic inhibition, leading to larger EPSPs and reduced action potential threshold. Our findings do not rule out, however, the possibility that modulation of voltage-gated conductances also contributes to E-S potentiation.

Action Potentials↗
PubMed2002

Serotonin receptor activation inhibits sodium current and dendritic excitability in prefrontal cortex via a protein kinase C-dependent mechanism.

The serotonin (5-HT) innervation of the prefrontal cortex (PFC) exerts a powerful modulatory influence on neuronal activity in this cortical region, although the mechanisms through which 5-HT modulates cellular activity are unclear. Voltage-dependent Na+ channels are one potential target of 5-HT receptor signaling that have wide-ranging effects on activity. Molecular and electrophysiological studies were used to test this potential linkage. Single cell RT-PCR profiling revealed that the vast majority of pyramidal neurons expressed detectable levels of 5-HT2a and/or 5-HT2c receptor mRNA with half of the cells expressing both mRNAs. Whole-cell voltage-clamp recordings of dissociated pyramidal neurons showed that 5-HT2a/c receptor activation reduced rapidly inactivating Na+ currents by reducing maximal current amplitude and shifting fast inactivation voltage dependence. These effects were mediated by G(q) activation of phospholipase C, leading to activation of protein kinase C (PKC). 5-HT2a/c receptor stimulation also reduced the amplitude of persistent Na+ current without altering its activation voltage dependence. This modulation was also mediated by PKC. Although 5-HT(2a,c) receptor activation did not affect somatic action potentials of layer V pyramidal neurons in PFC slices, it did reduce the amplitude of action potentials backpropagating into the apical dendrite. These findings show that 5-HT2a,c receptor activation reduces dendritic excitability and may negatively modulate activity-dependent dendritic synaptic plasticity.

Action Potentials↗
PubMed2002

Dendritic spikes as a mechanism for cooperative long-term potentiation.

Strengthening of synaptic connections following coincident pre- and postsynaptic activity was proposed by Hebb as a cellular mechanism for learning. Contemporary models assume that multiple synapses must act cooperatively to induce the postsynaptic activity required for hebbian synaptic plasticity. One mechanism for the implementation of this cooperation is action potential firing, which begins in the axon, but which can influence synaptic potentiation following active backpropagation into dendrites. Backpropagation is limited, however, and action potentials often fail to invade the most distal dendrites. Here we show that long-term potentiation of synapses on the distal dendrites of hippocampal CA1 pyramidal neurons does require cooperative synaptic inputs, but does not require axonal action potential firing and backpropagation. Rather, locally generated and spatially restricted regenerative potentials (dendritic spikes) contribute to the postsynaptic depolarization and calcium entry necessary to trigger potentiation of distal synapses. We find that this mechanism can also function at proximal synapses, suggesting that dendritic spikes participate generally in a form of synaptic potentiation that does not require postsynaptic action potential firing in the axon.

Action Potentials↗