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The cellular mechanisms of spike-frequency adaptation during prolonged discharges and of the slow afterhyperpolarization (AHP) that follows, as occur in vivo with contrast adaptation, were investigated with intracellular recordings of cortical neurons in slices of ferret primary visual cortex. Intracellular injection of 2 Hz sinusoidal or constant currents for 20 sec resulted in a slow (tau = 1-10 sec) spike-frequency adaptation, the degree of which varied widely among neurons. Reducing either [Ca(2+)](o) or [Na(+)](o) reduced the rate of spike-frequency adaptation. After the prolonged discharge was a slow (12-75 sec) AHP that was associated with an increase in membrane conductance and a rightward shift in the discharge frequency versus injected current relationship. The reversal potential of the slow AHP was sensitive to changes in [K(+)](o), indicating that it was mediated by a K(+) current. Blockade of transmembrane Ca(2+) conductances did not reduce the slow AHP. In contrast, reductions of [Na(+)](o) reduced the slow AHP, even in the presence of pronounced Ca(2+) spikes. We suggest that the activation of Na(+)-activated and Ca(2+)-activated K(+) currents plays an important role in prolonged spike-frequency adaptation and therefore may contribute to contrast adaptation and other forms of adaptation in the visual system in vivo.

Contrast adaptation is a psychophysical phenomenon, the neuronal bases of which reside largely in the primary visual cortex. The cellular mechanisms of contrast adaptation were investigated in the cat primary visual cortex in vivo through intracellular recording and current injections. Visual cortex cells, and to a much less extent, dorsal lateral geniculate nucleus (dLGN) neurons, exhibited a reduction in firing rate during prolonged presentations of a high-contrast visual stimulus, a process we termed high-contrast adaptation. In a majority of cortical and dLGN cells, the period of adaptation to high contrast was followed by a prolonged (5-80 sec) period of reduced responsiveness to a low-contrast stimulus (postadaptation suppression), an effect that was associated, and positively correlated, with a hyperpolarization of the membrane potential and an increase in apparent membrane conductance. In simple cells, the period of postadaptation suppression was not consistently associated with a decrease in the grating modulated component of the evoked synaptic barrages (the F1 component). The generation of the hyperpolarization appears to be at least partially intrinsic to the recorded cells, because the induction of neuronal activity with the intracellular injection of current resulted in both a hyperpolarization of the membrane potential and a decrease in the spike response to either current injections or visual stimuli. Conversely, high-contrast visual stimulation could suppress the response to low-intensity sinusoidal current injection. We conclude that control of the membrane potential by intrinsic neuronal mechanisms contributes importantly to the adaptation of neuronal responsiveness to varying levels of contrast. This feedback mechanism, internal to cortical neurons, provides them with the ability to continually adjust their responsiveness as a function of their history of synaptic and action potential activity.

Perigeniculate neurons form an interactive sheet of cells that inhibit one another as well as thalamocortical neurons in the dorsal lateral geniculate nucleus (LGNd). The inhibitory influence of the GABAergic neurons of the perigeniculate nucleus (PGN) onto other PGN neurons was examined with intracellular recordings in vitro. Intracellular recordings from PGN neurons during the generation of spindle waves revealed barrages of EPSPs and IPSPs. The excitation of local regions of the PGN with the local application of glutamate resulted in activation of IPSPs in neighboring PGN neurons. These IPSPs displayed an average reversal potential of -77 mV and were blocked by application of bicuculline methiodide or picrotoxin, indicating that they are mediated by GABAA receptors. In the presence of GABAA receptor blockade, the activation of PGN neurons with glutamate could result in slow IPSPs that were mediated by GABAB receptors in a subset (40%) of cells. Similarly, application of specific agonists muscimol and baclofen demonstrated that PGN neurons possess both functional GABAA and GABAB receptors. Examination of the axon arbors of biocytin-filled PGN neurons often revealed the presence of beaded axon collaterals within the PGN, suggesting that this may be an anatomical substrate for PGN to PGN inhibition. Functionally, activation of inhibition between PGN neurons could result in a shortening or a complete abolition of the low threshold Ca2+ spike or an inhibition of tonic discharge. We suggest that the mutual inhibition between PGN neurons forms a mechanism by which the excitability of these cells is tightly controlled. The activation of a point within the PGN may result in the inhibition of neighboring PGN neurons. This may be reflected in the LGNd as a center of inhibition surrounded by an annulus of disinhibition, thus forming a "center-surround" mechanism for thalamic function.

The properties of the inhibitory influence of neurons in the perigeniculate (PGN) nucleus on thalamocortical cells were examined with intracellular recordings in the ferret geniculate slice maintained in vitro. Activation of PGN neurons with the local application of glutamate caused IPSPs in thalamocortical neurons that were mediated by both GABAA and GABAB receptors, as well as the activation of spindle waves. With low intensity stimulation of the PGN, local application of bicuculline to the dorsal lateral geniculate nucleus (LGNd) strongly inhibited evoked and spindle-associated IPSPs, indicating that these are largely mediated by GABAA receptors. The generation of GABAB receptor-mediated IPSPs in thalamocortical cells that were large enough to generate rebound low threshold Ca2+ spikes required substantially increased activation of the PGN with glutamate. The activation of synchronous bicuculline-induced slowed oscillations in thalamocortical neurons required the block of GABAA receptors in the LGNd as well as in the PGN. These results indicate that bursts of action potentials in PGN neurons can result in the activation of both GABAA and GABAB receptors in thalamocortical neurons, with the strong activation of GABAB receptors requiring an intense, simultaneous discharge of a number of PGN neurons. Functionally, these results suggest that PGN neurons inhibit thalamocortical cells preferentially through the activation of GABAA receptors, although the strong activation of GABAB receptors may occur under pathological conditions and contribute to the generation of abnormal, synchronous slow oscillations.

The ferret dorsal lateral geniculate nucleus (LGNd) contains interneurons within the interlaminar zones situated between the laminae corresponding to the ipsi- and contralateral eyes. We found that a subset of these neurons exhibits electrophysiological properties similar to those previously reported for perigeniculate (PGN) neurons, including the generation of rhythmic sequences of rebound low-threshold Ca2+ spikes at a frequency of 1-4 Hz after the intracellular injection of a hyperpolarizing current pulse. These "PGN-like" interlaminar interneurons innervated restricted regions of the A-laminae, inhibited thalamocortical cells through GABAA, and perhaps GABAB, receptors, and were excited by axon collaterals from thalamocortical cells. This reciprocal relationship is identical to that formed by PGN cells and allowed the PGN-like interlaminar neurons to participate in the generation of spindle waves and other network oscillations. Pharmacologically, PGN-like interlaminar interneurons were also similar to PGN neurons: both generated a prolonged depolarization in response to the local application of serotonin, 1S,3R-ACPD, and CCK8S, and a rapid depolarization followed by a more prolonged hyperpolarization in response to acetylcholine. Examination of parvalbumin and calbindin staining in the ferret LGNd revealed that both PGN and a subset of interlaminar neurons were parvalbumin-positive. In contrast, calbindin-positive cells were relatively absent in the PGN and sparsely present in the interlaminar zones, but were numerous in the A and C laminae. Our results indicate that the interlaminar zone in between laminae A and A1 and A1 and C in the ferret LGNd possesses a cell type that is electrophysiologically, pharmacologically, anatomically, immunocytochemically, and functionally similar to neurons in the PGN.