Biomedical subjects

Pablo Fuentealba

Publications and source records attributed to Pablo Fuentealba.

8 recordsLinked to original sources

PubMed2005

Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations.

In the hippocampal CA1 area, a relatively homogenous population of pyramidal cells is accompanied by a diversity of GABAergic interneurons. Previously, we found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells, innervating different domains of pyramidal cells, have distinct firing patterns during network oscillations in vivo. A second family of interneurons, expressing cholecystokinin but not parvalbumin, is known to target the same domains of pyramidal cells as do the parvalbumin cells. To test the temporal activity of these independent and parallel GABAergic inputs, we recorded the precise spike timing of identified cholecystokinin interneurons during hippocampal network oscillations in anesthetized rats and determined their molecular expression profiles and synaptic targets. The cells were cannabinoid receptor type 1 immunopositive. Contrary to the stereotyped firing of parvalbumin interneurons, cholecystokinin-expressing basket and dendrite-innervating cells discharge, on average, with 1.7 +/- 2.0 Hz during high-frequency ripple oscillations in an episode-dependent manner. During theta oscillations, cholecystokinin-expressing interneurons fire with 8.8 +/- 3.3 Hz at a characteristic time on the ascending phase of theta waves (155 +/- 81 degrees), when place cells start firing in freely moving animals. The firing patterns of some interneurons recorded in drug-free behaving rats were similar to cholecystokinin cells in anesthetized animals. Our results demonstrate that cholecystokinin- and parvalbumin-expressing interneurons make different contributions to network oscillations and play distinct roles in different brain states. We suggest that the specific spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids might contribute to differentiate subgroups of pyramidal cells forming neuronal assemblies, whereas parvalbumin interneurons contribute to synchronizing the entire network.

Action Potentials↗

PubMed2005

Synaptic plasticity in local cortical network in vivo and its modulation by the level of neuronal activity.

Neocortical neurons maintain high firing rates across all behavioral states of vigilance but the discharge patterns vary during different types of brain oscillations, which are assumed to play an important role in information processing and memory consolidation. In the present study, we report that trains of stimuli applied to local neocortical networks of cats, at frequencies that mimic endogenous brain rhythms, produced depression or potentiation of postsynaptic potentials, which lasted for several minutes. This form of synaptic plasticity was not mediated through NMDA receptors since it persisted after blockade of these receptors, but was strongly modulated by the level of background neuronal activity. Using different preparations in vivo, we found that increased background neuronal activity decreased the probability of plastic changes but enhanced the probability of potentiation over depression. Conversely, when the level of background neuronal activity was low, plasticity was observed in all neurons, but mainly depression was induced. Our results demonstrate that high levels of neuronal activity in the cortical network promote potentiation and insure the stability of synaptic connections.

Anesthesia↗

PubMed2005

The reticular nucleus revisited: intrinsic and network properties of a thalamic pacemaker.

The intrinsic and network properties of thalamic reticular (RE) neurons, which release the potent inhibitory neurotransmitter gamma-aminobutyric acid (GABA), endow them with oscillatory properties within the frequency range of sleep spindles (7-15 Hz), a hallmark brain rhythm that characterizes early sleep stages. The original hypothesis that RE neurons are pacemakers of spindles, based on absence of this oscillation in thalamocortical (TC) systems after disconnection from RE nucleus and presence of spindle rhythmicity in the deafferented RE nucleus, is supported by new experimental results in vivo, in vitro and in computo showing that interactions through chemical synapses as well as electrical coupling among inhibitory RE neurons lead to generation and synchronization of spindle sequences within the nucleus. Besides their pacemaking role in spindle generation, RE neurons are crucially implicated in the inhibition of TC neurons during cortically generated spike-wave (absence) seizures, which may explain the obliteration of signals from the external world and unconsciousness during these epileptic fits.

Biological Clocks↗

PubMed2004

Membrane bistability in thalamic reticular neurons during spindle oscillations.

The thalamic reticular (RE) nucleus is a major source of inhibition in the thalamus. It plays a crucial role in regulating the excitability of thalamocortical networks and in generating some sleep rhythms. Current-clamp intracellular recordings of RE neurons in cats under barbiturate anesthesia revealed the presence of membrane bistability in approximately 20% of neurons. Bistability consisted of two alternate membrane potentials, separated by approximately 17-20 mV. While non-bistable (common) RE neurons fired rhythmic spike-bursts during spindles, bistable RE neurons fired tonically, with burst modulation, throughout spindle sequences. Bistability was strongly voltage dependent and only expressed under resting conditions (i.e. no current injection). The transition from the silent to the active state was a regenerative event that could be activated by brief depolarization, whereas brief hyperpolarizations could switch the membrane potential from the active to the silent state. These effects outlasted the current pulses. Corticothalamic stimulation could also switch the membrane potential from silent to active states. Addition of QX-314 in the recording micropipette either abolished or disrupted membrane bistability, suggesting I(Na(p)) to be responsible for its generation. Thalamocortical cells presented various patterns of spindling that reflected the membrane bistability in RE neurons. Finally, experimental data and computer simulations predicted a role for RE neurons' membrane bistability in inducing various patterns of spindling in target thalamocortical cells. We conclude that membrane bistability of RE neurons is an intrinsic property, likely generated by I(Na(p)) and modulated by cortical influences, as well as a factor that determines different patterns of spindle rhythms in thalamocortical neurons.

Action Potentials↗

PubMed2004

Prolonged hyperpolarizing potentials precede spindle oscillations in the thalamic reticular nucleus.

The thalamic reticular (RE) nucleus is a key structure in the generation of spindles, a hallmark bioelectrical oscillation during early stages of sleep. Intracellular recordings of RE neurons in vivo revealed the presence of prolonged hyperpolarizing potentials preceding spindles in a subgroup (30%) of neurons. These hyperpolarizations (6-10 mV) lasted for 200-300 ms and were present just before the onset of spontaneously occurring spindle waves. Corticothalamic volleys also were effective in generating such hyperpolarizations followed by spindles in RE neurons. A drop of up to 40% in the apparent input resistance (R(in)) was associated with these hyperpolarizing potentials, suggesting an active process rather than disfacilitation. Accordingly, the reversal potential was approximately -100 mV for both spontaneous and cortically elicited hyperpolarizations, consistent with the activation of slow K(+) conductances. QX-314 in the recording pipettes decreased both the amplitude and incidence of prolonged hyperpolarizations, suggesting the participation of G protein-dependent K(+) currents in the generation of hyperpolarizations. Simultaneous extracellular and intracellular recordings in the RE nucleus demonstrated that some RE neurons discharged during the hyperpolarizations and, thus, may be implicated in their generation. The prolonged hyperpolarizations preceding spindles may play a role in the transition from tonic to bursting firing of RE neurons within a range of membrane potential (-60 to -65 mV) at which they set favorable conditions for the generation of low-threshold spike bursts that initiate spindle sequences. These data are further arguments for the generation of spindles within the thalamic RE nucleus.

Action Potentials↗

PubMed2004

Experimental evidence and modeling studies support a synchronizing role for electrical coupling in the cat thalamic reticular neurons in vivo.

Thalamic reticular (RE) neurons are crucially implicated in brain rhythms. Here, we report that RE neurons of adult cats, recorded and stained intracellularly in vivo, displayed spontaneously occurring spikelets, which are characteristic of central neurons that are coupled electrotonically via gap junctions. Spikelets occurred spontaneously during spindles, an oscillation in which RE neurons play a leading role, as well as during interspindle lulls. They were significantly different from excitatory postsynaptic potentials and also distinct from fast prepotentials that are presumably dendritic spikes generated synaptically. Spikelets were strongly reduced by halothane, a blocker of gap junctions. Multi-site extracellular recordings performed before, during and after administration of halothane demonstrated a role for electrical coupling in the synchronization of spindling activity within the RE nucleus. Finally, computational models of RE neurons predicted that gap junctions between these neurons could mediate the spread of low-frequency activity at great distances. These experimental and modeling data suggest that electrotonic coupling within the RE nucleus plays an important role in the generation and synchronization of low-frequency (spindling) activities in the thalamus.

Action Potentials↗

PubMed2004

The cortically evoked secondary depolarization affects the integrative properties of thalamic reticular neurons.

Corticothalamic terminals on thalamic reticular (RE) neurons account for most synapses from afferent pathways onto this nucleus and these inputs are more powerful than those from axon collaterals of thalamocortical neurons. Given the supremacy of cortical inputs, we analysed here the characteristics and possible mechanisms underlying a secondary component of the cortically elicited depolarization in RE neurons, recorded in cats under barbiturate anesthesia. Electrical stimulation of corticothalamic axons in the internal capsule evoked fixed and short-latency excitatory postsynaptic potentials (EPSPs) that, by increasing stimulation intensity and at hyperpolarized levels (< -70 mV), developed into low-threshold spikes and spindle oscillations. The threshold for spindle oscillations was 60% higher than that required for evoking minimal EPSPs. The evoked EPSPs included a secondary depolarizing component, which appeared approximately 5 ms after the peak of the initial component and was voltage dependent, i.e. most prominent between -70 mV and -85 mV, while being greatly reduced or absent at more hyperpolarized levels. The secondary depolarizing component was sensitive to QX-314 in the recording micropipette. We suggest that the secondary component of cortically evoked EPSPs in RE neurons is due to the dendritic activation of T-currents, with a probable contribution of the persistent Na+ current. This late component affected the integrative properties of RE neurons, including their spiking output and temporal summation of incoming cortical inputs.

Anesthetics, Local↗

PubMed2004

Synaptic interactions between thalamic and cortical inputs onto cortical neurons in vivo.

To study the interactions between thalamic and cortical inputs onto neocortical neurons, we used paired-pulse stimulation (PPS) of thalamic and cortical inputs as well as PPS of two cortical or two thalamic inputs that converged, at different time intervals, onto intracellularly recorded cortical and thalamocortical neurons in anesthetized cats. PPS of homosynaptic cortico-cortical pathways produced facilitation, depression, or no significant effects in cortical pathways, whereas cortical responses to thalamocortical inputs were mostly facilitated at both short and long intervals. By contrast, heterosynaptic interactions between either cortical and thalamic, or thalamic and cortical, inputs generally produced decreases in the peak amplitudes and depolarization area of evoked excitatory postsynaptic potentials (EPSPs), with maximal effect at approximately 10 ms and lasting from 60 to 100 ms. All neurons tested with thalamic followed by cortical stimuli showed a decrease in the apparent input resistance (R(in)), the time course of which paralleled that of decreased responses, suggesting that shunting is the factor accounting for EPSP's decrease. Only half of neurons tested with cortical followed by thalamic stimuli displayed changes in R(in). Spike shunting in the thalamus may account for those cases in which decreased synaptic responsiveness of cortical neurons was not associated with decreased R(in) because thalamocortical neurons showed decreased firing probability during cortical stimulation. These results suggest a short-lasting but strong shunting between thalamocortical and cortical inputs onto cortical neurons.

Action Potentials↗