RESUMEN
Memories are acquired and encoded within large-scale neuronal networks spanning different brain areas. The anatomical and functional specificity of such long-range interactions and their role in learning is poorly understood. The amygdala and the medial prefrontal cortex (mPFC) are interconnected brain structures involved in the extinction of conditioned fear. Here, we show that a defined subpopulation of basal amygdala (BA) projection neurons targeting the prelimbic (PL) subdivision of mPFC is active during states of high fear, whereas BA neurons targeting the infralimbic (IL) subdivision are recruited, and exhibit cell-type-specific plasticity, during fear extinction. Pathway-specific optogenetic manipulations demonstrate that the activity balance between pathways is causally involved in fear extinction. Together, our findings demonstrate that, although intermingled locally, long-range connectivity defines distinct subpopulations of amygdala projection neurons and indicate that the formation of long-term extinction memories depends on the balance of activity between two defined amygdala-prefrontal pathways.
Asunto(s)
Amígdala del Cerebelo/citología , Vías Nerviosas/fisiología , Neuronas/fisiología , Estimulación Acústica/efectos adversos , Potenciales de Acción/genética , Potenciales de Acción/fisiología , Análisis de Varianza , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Fenómenos Biofísicos/efectos de los fármacos , Fenómenos Biofísicos/fisiología , Biofisica , Recuento de Células , Channelrhodopsins , Condicionamiento Clásico , Venenos Elapídicos/farmacología , Estimulación Eléctrica , Extinción Psicológica , Miedo/psicología , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/metabolismo , Hipocampo/citología , Hipocampo/fisiología , Técnicas In Vitro , Luz , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Masculino , Ratones , Proteínas Oncogénicas v-fos/metabolismo , Optogenética , Técnicas de Placa-Clamp , Péptidos/farmacología , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Factores de TiempoRESUMEN
Intracellular recordings from association cortical areas 5 and 7 were performed in cats under barbiturate or ketamine-xylazine anesthesia to investigate the activities of different classes of neurons involved in callosal pathways, which were electrophysiologically characterized by depolarizing current steps. Excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and/or antidromic responses were elicited by stimulating homotopic sites in the contralateral cortical areas. Differential features of EPSPs related to latencies, amplitudes, and slopes were detected in closely located (50 microm or less) neurons recorded in succession along the same electrode track. In contrast to synchronous thalamocortical volleys that excited most neurons within a cortical column, stimuli applied to homotopic sites in the contralateral cortex activated neurons at restricted cortical depths. Median latencies of callosally evoked EPSPs were 1.5 to 4 ms in various cortical cell-classes. Fast-rhythmic-bursting neurons displayed EPSPs whose amplitudes were threefold larger, and latencies two- or threefold shorter, than those found in the three other cellular classes. Converging callosal and thalamic inputs were recorded in the same cortical neuron. EPSPs or IPSPs were elicited by stimulating foci spaced by <1 mm in the contralateral cortex. In the overwhelming majority of neurons, latencies of antidromic responses were between 1.2 and 3.1 ms; however, some callosal neurons had much longer latencies, Asunto(s)
Corteza Cerebral/citología
, Corteza Cerebral/fisiología
, Cuerpo Calloso/citología
, Cuerpo Calloso/fisiología
, Neuronas/fisiología
, Animales
, Gatos
, Potenciales Postsinápticos Excitadores/fisiología
, Inhibición Neural/fisiología
, Vías Nerviosas
, Tálamo/citología
, Tálamo/fisiología
RESUMEN
Thalamic stimulation at frequencies between 5 and 15 Hz elicits incremental or 'augmenting' cortical responses. Augmenting responses can also be evoked in cortical slices and isolated cortical slabs in vivo. Here we show that a realistic network model of cortical pyramidal cells and interneurones including short-term plasticity of inhibitory and excitatory synapses replicates the main features of augmenting responses as obtained in isolated slabs in vivo. Repetitive stimulation of synaptic inputs at frequencies around 10 Hz produced postsynaptic potentials that grew in size and carried an increasing number of action potentials resulting from the depression of inhibitory synaptic currents. Frequency selectivity was obtained through the relatively weak depression of inhibitory synapses at low frequencies, and strong depression of excitatory synapses together with activation of a calcium-activated potassium current at high frequencies. This network resonance is a consequence of short-term synaptic plasticity in a network of neurones without intrinsic resonances. These results suggest that short-term plasticity of cortical synapses could shape the dynamics of synchronized oscillations in the brain.