Multielectrode Recordings From Identified Neurons Involved in Visually Elicited Escape Behavior

A major challenge in current neuroscience is to understand the concerted functioning of distinct neurons involved in a particular behavior. This goal first requires achieving an adequate characterization of the behavior as well as an identification of the key neuronal elements associated with that action. Such conditions have been considerably attained for the escape response to visual stimuli in the crab Neohelice. During the last two decades a combination of in vivo intracellular recordings and staining with behavioral experiments and modeling, led us to postulate that a microcircuit formed by four classes of identified lobula giant (LG) neurons operates as a decision-making node for several important visually-guided components of the crab’s escape behavior. However, these studies were done by recording LG neurons individually. To investigate the combined operations performed by the group of LG neurons, we began to use multielectrode recordings. Here we describe the methodology and show results of simultaneously recorded activity from different lobula elements. The different LG classes can be distinguished by their differential responses to particular visual stimuli. By comparing the response profiles of extracellular recorded units with intracellular recorded responses to the same stimuli, two of the four LG classes could be faithfully recognized. Additionally, we recorded units with stimulus preferences different from those exhibited by the LG neurons. Among these, we found units sensitive to optic flow with marked directional preference. Units classified within a single group according to their response profiles exhibited similar spike waveforms and similar auto-correlograms, but which, on the other hand, differed from those of groups with different response profiles. Additionally, cross-correlograms revealed excitatory as well as inhibitory relationships between recognizable units. Thus, the extracellular multielectrode methodology allowed us to stably record from previously identified neurons as well as from undescribed elements of the brain of the crab. Moreover, simultaneous multiunit recording allowed beginning to disclose the connections between central elements of the visual circuits. This work provides an entry point into studying the neural networks underlying the control of visually guided behaviors in the crab brain.Fil: Cámera, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Belluscio, Mariano Andres. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tomsic, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Closed-loop control of epilepsy by transcranial electrical stimulation

Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients.Fil: Berényi, Antal. Rutgers University; Estados Unidos. University of New York; Estados Unidos. University of Szeged; HungríaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Rutgers University; Estados UnidosFil: Mao, Dun. Rutgers University; Estados UnidosFil: Buzsáki, György. Rutgers University; Estados Unidos. University of New York; Estados Unido

Cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

Neuronal oscillations allow for temporal segmentation of neuronal spikes. Interdependent oscillators can integrate multiple layers of information. We examined phase–phase coupling of theta and gamma oscillators in the CA1 region of rat hippocampus during maze exploration and rapid eye movement sleep. Hippocampal theta waves were asymmetric, and estimation of the spatial position of the animal was improved by identifying the waveform-based phase of spiking, compared to traditional methods used for phase estimation. Using the waveform-based theta phase, three distinct gamma bands were identified: slow gammaS (gammaS; 30–50 Hz), midfrequency gammaM (gammaM; 50–90 Hz), and fast gammaF (gammaF; 90–150 Hz or epsilon band). The amplitude of each sub-band was modulated by the theta phase. In addition, we found reliable phase–phase coupling between theta and both gammaS and gammaM but not gammaF oscillators. We suggest that cross-frequency phase coupling can support multiple time-scale control of neuronal spikes within and across structures.Fil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mizuseki, Kenji. Rutgers University; Estados UnidosFil: Schmidt, Robert. Rutgers University; Estados UnidosFil: Kempter, Richard. Rutgers University; Estados UnidosFil: Buzsáki, György. Rutgers University; Estados Unido

Dorsal striatum coding for the timely execution of action sequences

The automatic initiation of actions can be highly functional. But occasionally these actions cannot be withheld and are released at inappropriate times, impulsively. Striatal activity has been shown to participate in the timing of action sequence initiation and it has been linked to impulsivity. Using a self- initiated task, we trained adult rats to withhold a rewarded action sequence until a waiting time interval has elapsed. By analyzing neuronal activity we show that the striatal response preceding the initiation of the learned sequence is strongly modulated by the time subjects wait before eliciting the sequence. Interestingly, the modulation is steeper in adolescent rats, which show a strong prevalence of impulsive responses compared to adults. We hypothesize this anticipatory striatal activity reflects the animals? subjective reward expectation, based on the elapsed waiting time, while its steeper waiting modulation in adolescence reflects age-related differences in temporal discounting, internal urgency states or explore- exploit balance.Fil: Martínez, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Zold, Camila Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Volume-Conducted Origin of the Field Potential at the Lateral Habenula

Field potentials (FPs) are easily reached signals that provide information about the brain’s processing. However, FP should be interpreted cautiously since their biophysical bases are complex. The lateral habenula (LHb) is a brain structure involved in the encoding of aversive motivational values. Previous work indicates that the activity of the LHb is relevant for hippocampal-dependent learning. Moreover, it has been proposed that the interaction of the LHb with the hippocampal network is evidenced by the synchronization of LHb and hippocampal FPs during theta rhythm. However, the origin of the habenular FP has not been analyzed. Hence, its validity as a measurement of LHb activity has not been proven. In this work, we used electrophysiological recordings in anesthetized rats and feed-forward modeling to investigate biophysical basis of the FP recorded in the LHb. Our results indicate that the FP in the LHb during theta rhythm is a volume-conducted signal from the hippocampus. This result highlight that FPs must be thoroughly analyzed before its biological interpretation and argues against the use of the habenular FP signal as a readout of the activity of the LHb.Fil: Bertone Cueto, Nicolas Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Makarova, Julia. Consejo Superior de Investigaciones Científicas; EspañaFil: Mosqueira, Alejo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: García Violini, Demian. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Herreras, Oscar. Consejo Superior de Investigaciones Científicas; EspañaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Piriz, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Brain oscillations, medium spiny neurons, and dopamine

1. The striatum is part of a multisynaptic loop involved in translating higher order cognitive activity into action. The main striatal computational unit is the medium spiny neuron, which integrates inputs arriving from widely distributed cortical neurons and provides the sole striatal output. 2. The membrane potential of medium spiny neurons’ displays shifts between a very negative resting state (down state) and depolarizing plateaus (up states) which are driven by the excitatory cortical inputs. 3. Because striatal spiny neurons fire action potentials only during the up state, these plateau depolarizations are perceived as enabling events that allow information processing through cerebral cortex – basal ganglia circuits. In vivo intracellular recording techniques allow to investigate simultaneously the subthreshold behavior of the medium spiny neuron membrane potential (which is a “reading” of distributed patterns of cortical activity) and medium spiny neuron firing (which is an index of striatal output). 4. Recent studies combining intracellular recordings of striatal neurons with field potential recordings of the cerebral cortex illustrate how the analysis of the input–output transformations performed by medium spiny neurons may help to unveil some aspects of information processing in cerebral cortex – basal ganglia circuits, and to understand the origin of the clinical manifestations of Parkinson’s disease and other neurologic and neuropsychiatric disorders that result from alterations in dopamine-dependent information processing in the cerebral cortex – basal ganglia circuits.Fil: Murer, Mario Gustavo. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Tseng, Kuei Y.. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Kasanetz, Fernando. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Belluscio, Mariano Andres. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Riquelme, Luis Alberto. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Oscillations in the basal ganglia in Parkinson's disease: Role of the striatum

In animal models of Parkinson´s disease cortical oscillations entrain abnormal synchronous rhythms in basal ganglia neurons. A mechanism accounting for these oscillations should: (i) vindicate a key role of the striatum in Parkinson´s disease pathophysiology by considering how alterations in striatal physiology may gate cortico-basal ganglia oscillations; (ii) explain why abnormal basal ganglia oscillations span the whole frequency range of oscillations observed in the normal frontal cortex; and (iii) provide insight into how these oscillations may relate to akinesia. Here we update our proposal that striatal projection neurons (medium spiny neurons) behave as dopamine-dependent filters which normally do not allow the propagation of resting cortical activity through the basal ganglia circuit. After chronic dopamine depletion, cortical oscillations would spread through more excitable medium spiny neurons to entrain the whole indirect pathway. Therefore, akinesia may not be directly related to oscillations, but to the inability of medium spiny neurons to separate salient pieces of cortical information from the ongoing cortical rhythms they are embedded in. We propose that uncontrolled translation of ongoing cortical activity into no-go signals in the indirect pathway induces akinesia. Thus, oscillations would be an extreme manifestation of this excessive permeability of medium spiny neurons to cortical input in advanced stages of Parkinson´s disease.Fil: Belluscio, Mariano Andres. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiología de Circuitos Neuronales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Escande, Mariela Veronica. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiología de Circuitos Neuronales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Keifman, Ettel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiología de Circuitos Neuronales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Riquelme, Luis Alberto. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiología de Circuitos Neuronales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Murer, Mario Gustavo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiología de Circuitos Neuronales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zold, Camila Lidia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiología de Circuitos Neuronales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Classification based on dynamic mode decomposition applied to brain recognition of context

Local Field Potentials (LFPs) are easy to access electrical signals of the brain that represent the summation in the extracellular space, of currents originated within the neurons. As such, LFPs could contain information about ongoing computations in neuronal circuits and could potentially be used to design brain machine interface algorithms. However how brain computations could be decoded from LFPs is not clear. Within this context, a methodology for signal classification is proposed in this study, particularly based on the Dynamic Mode Decomposition method, in conjunction with binary clustering routines based on supervised learning. Note that, although the classification methodology is presented here in the context of a biological problem, it can be applied to a broad range of applications. Then, as a case-study, the proposed method is validated with the classification of LFP-based brain cognitive states. All the analysis, signals, and results shown in this study consider real data measured in the hippocampus, in rats performing exploration tasks. Consequently, it is shown that, using the measured LFP, the method infers which context was the animal exploring. Thus, evidence on the spatial codification in LFP signals is consequently provided, which still is an open question in neuroscience.Fil: Martínez, Sebastián. Instituto Tecnológico de Buenos Aires; ArgentinaFil: Silva, Azul. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: García Violini, Diego Demián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Piriz, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Tecnológico de Buenos Aires; Argentin

Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism

Motor execution and planning are tightly regulated by dopamine D1 and D2 receptors present in basal ganglia circuits. Although stimulation of D1 receptors is known to enhance motor function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversial, with studies showing increasing, decreasing or no changes in motor activity. Moreover, pharmacological and genetic attempts to block or eliminate D2R have led to controversial results that questioned the importance of D2R in motor function. In this study, we generated an inducible Drd2 null-allele mouse strain that circumvented developmental compensations found in constitutive Drd2−/− mice and allowed us to directly evaluate the participation of D2R in spontaneous locomotor activity and motor learning. We have found that loss of D2R during adulthood causes severe motor impairments, including hypolocomotion, deficits in motor coordination, impaired learning of new motor routines and spontaneous catatonia. Moreover, severe motor impairment, resting tremor and abnormal gait and posture, phenotypes reminiscent of Parkinson’s disease, were evident when the mutation was induced in aged mice. Altogether, the conditional Drd2 knockout model studied here revealed the overall fundamental contribution of D2R in motor functions and explains some of the side effects elicited by D2R blockers when used in neurological and psychiatric conditions, including schizophrenia, bipolar disorder, Tourette’s syndrome, dementia, alcohol-induced delusions and obsessive-compulsive disorder.Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Casas Cordero, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Galiñanes, Gregorio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Casey, Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Rodríguez, V. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentin