David J. Perkel

Revised Nomenclature for Avian Telencephalon and Some Related Brainstem Nuclei

The standard nomenclature that has been used for many telencephalic and related brainstem structures in birds is based on flawed assumptions of homology to mammals. In particular, the outdated terminology implies that most of the avian telencephalon is a hypertrophied basal ganglia, when it is now clear that most of the avian telencephalon is neurochemically, hodologically, and functionally comparable to the mammalian neocortex, claustrum, and pallial amygdala (all of which derive from the pallial sector of the developing telencephalon). Recognizing that this promotes misunderstanding of the functional organization of avian brains and their evolutionary relationship to mammalian brains, avian brain specialists began discussions to rectify this problem, culminating in the Avian Brain Nomenclature Forum held at Duke University in July 2002, which approved a new terminology for avian telencephalon and some allied brainstem cell groups. Details of this new terminology are presented here, as is a rationale for each name change and evidence for any homologies implied by the new names.

Avian brains and a new understanding of vertebrate brain evolution

We believe that names have a powerful influence on the experiments we do and the way in which we think. For this reason, and in the light of new evidence about the function and evolution of the vertebrate brain, an international consortium of neuroscientists has reconsidered the traditional, 100-year-old terminology that is used to describe the avian cerebrum. Our current understanding of the avian brain — in particular the neocortex-like cognitive functions of the avian pallium — requires a new terminology that better reflects these functions and the homologies between avian and mammalian brains.

Analysis of excitatory synaptic action in pyramidal cells using whole‐cell recording from rat hippocampal slices.

1. The pharmacological and biophysical properties of excitatory synapses in the CA1 region of the hippocampus were studied using patch electrodes and whole‐cell recording from thin slices. 2. Excitatory postsynaptic currents (EPSCs) had a fast component whose amplitude was voltage insensitive and a slow component whose amplitude was voltage dependent with a region of negative slope resistance in the range of ‐70 to ‐30 mV. 3. The voltage‐dependent component was abolished by the N‐methyl‐D‐aspartate (NMDA) receptor antagonist DL‐2‐amino‐5‐phosphonovalerate (APV; 50 microM), which had no effect on the fast component. Conversely, the fast voltage‐insensitive component was abolished by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 10 microM) which had no effect on the slow component. 4. In Ringer solution with no added Mg2+ the current‐voltage relation of the NMDA component was linear over a much larger voltage range than in the presence of 1.3 mM‐Mg2+. 5. The NMDA component of the EPSC could be switched off with a hyperpolarizing voltage step at the soma. The kinetics of this switch‐off was used to estimate the speed of clamp control of the subsynaptic membrane as well as the electrotonic distance from the soma. The kinetic analysis of the EPSC was restricted to synapses which were judged to be under adequate voltage control. 6. For those synapses that were close to the soma the time constant for decay for the non‐NMDA component, which was voltage insensitive, ranged from 4‐8 ms. 7. The rise time for the NMDA component was 8‐20 ms and the time constant for decay ranged from 60‐150 ms. 8. During increased transmitter release with post‐tetanic potentiation or application or phorbol esters, both components of the EPSC increased to a similar extent. 9. These experiments provide a detailed description of the dual receptor mechanism operating at hippocampal excitatory synapses. In addition, the experiments provide an electrophysiological method for estimating the electrotonic distance of synaptic inputs.

Excitatory synaptic currents in Purkinje cells.

The N-methyl-D-aspartate (NMDA) and non-NMDA classes of glutamate receptor combine in many regions of the central nervous system to form a dual-component excitatory postsynaptic current. Non-NMDA receptors mediate synaptic transmission at the resting potential, whereas NMDA receptors contribute during periods of postsynaptic depolarization and play a role in the generation of long-term synaptic potentiation. To investigate the receptor types underlying excitatory synaptic transmission in the cerebellum, we have recorded excitatory postsynaptic currents (EPSCS), by using whole-cell techniques, from Purkinje cells in adult rat cerebellar slices. Stimulation in the white matter or granule-cell layer resulted in an all-or-none synaptic current as a result of climbing-fibre activation. Stimulation in the molecular layer caused a graded synaptic current, as expected for activation of parallel fibres. When the parallel fibres were stimulated twice at an interval of 40 ms, the second EPSC was facilitated ; similar paired-pulse stimulation of the climbing fibre resulted in a depression of the second EPSC. Both parallel-fibre and climbing-fibre responses exhibited linear current-voltage relations. At a holding potential of -40 mV or in the nominal absence of Mg2+ these synaptic responses were unaffected by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV), but were blocked by the non-NMDA receptor antagonist 6-cyano-2, 3-dihydro-7-nitroquinoxalinedione (CNQX). NMDA applied to the bath failed to evoke an inward current, whereas aspartate or glutamate induced a substantial current; this current was, however, largely reduced by CNQX, indicating that non-NMDA receptors mediate this response. These results indicate that both types of excitatory input to adult Purkinje cells are mediated exclusively by glutamate receptors of the non-NMDA type, and that these cells entirely lack NMDA receptors.

The impact of postsynaptic calcium on synaptic transmission — its role in long-term potentiation

Recent studies have gone a long way to explain the steps involved in generating long-term potentiation (LTP). This review focuses on the triggering role of postsynaptic calcium, the sequence of events which might be initiated by calcium, and where the persistent change may ultimately occur during LTP.

Birdbrains could teach basal ganglia research a new song

Recent advances in anatomical, physiological and histochemical characterization of avian basal ganglia neurons and circuitry have revealed remarkable similarities to mammalian basal ganglia. A modern revision of the avian anatomical nomenclature has now provided a common language for studying the function of the cortical-basal-ganglia-cortical loop, enabling neuroscientists to take advantage of the specialization of basal ganglia areas in various avian species. For instance, songbirds, which learn their vocal motor behavior using sensory feedback, have specialized a portion of their cortical-basal ganglia circuitry for song learning and production. This discrete circuit dedicated to a specific sensorimotor task could be especially tractable for elucidating the interwoven sensory, motor and reward signals carried by basal ganglia, and the function of these signals in task learning and execution.

Evidence for all-or-none regulation of neurotransmitter release: implications for long-term potentiation.

1. We have used the whole‐cell patch‐clamp recording technique to examine the modulation of dual‐component excitatory postsynaptic currents (EPSCs) in CA1 pyramidal cells in guinea‐pig hippocampal slices. 2. The dramatic difference in the reported sensitivities of the N‐methyl‐D‐aspartate (NMDA) and non‐NMDA glutamate receptors to glutamate suggests that changes in transmitter concentration in the synaptic cleft would result in differential modulation of the two components of the EPSC. 3. To test whether presynaptic manipulations change transmitter concentration in the synaptic cleft, pharmacological modulation of transmitter release by the GABAB agonist baclofen or by the adenosine antagonist theophylline was used. These manipulations resulted in parallel changes of NMDA and non‐NMDA receptor‐mediated components of EPSCs over a sixteen‐fold range. 4. Stimuli that induce long‐term potentiation (LTP) did not cause a sustained enhancement of isolated NMDA receptor‐mediated EPSCs evoked in the presence of the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX). 5. To compare directly the effect of LTP on the components of the EPSC, dual‐component EPSCs were elicited while the postsynaptic membrane potential was held at +30 mV. Induction of long‐term potentiation by delivering low‐frequency synaptic stimulation in conjunction with such depolarization led to differential enhancement of the non‐NMDA receptor‐mediated component of the EPSC. 6. These data support the notion that synaptic transmission at individual boutons occurs in an all‐or‐none fashion, without changing peak transmitter concentration in the synaptic cleft. Long‐term potentiation could occur through a postsynaptic modification of receptors or through a presynaptic change involving increased transmitter concentration in the synaptic cleft, but is difficult to explain by a generalized increase in release probability.

The role of Ca2+ entry via synaptically activated NMDA receptors in the induction of long-term potentiation

Influx of Ca2+ through the NMDA subtype of glutamate receptor is widely accepted as a trigger for many forms of neural plasticity. However, direct support for this model has been elusive, since indirect activation of dendritic voltage-sensitive Ca2+ channels is difficult to exclude. We have optically measured synaptically induced changes in cytoplasmic free Ca2+ concentration in pyramidal cell dendrites in hippocampal slices. Steady postsynaptic depolarization to the synaptic reversal potential eliminated the effect of voltage-sensitive Ca2+ channels. Under these conditions, synaptically induced Ca2+ transients were observed, which were blocked by the NMDA receptor antagonist APV. In addition, the magnitude of LTP was diminished when induced with the postsynaptic membrane held at progressively more positive potentials. LTP could be completely suppressed at potentials near +100 mV. These results provide important experimental support for a role for Ca2+ influx through NMDA receptors in synaptic plasticity.

Songbirds and the revised Avian Brain Nomenclature

Abstract: It has become increasingly clear that the standard nomenclature for many telencephalic and related brainstem structures of the avian brain is based on flawed once‐held assumptions of homology to mammalian brain structures, greatly hindering functional comparisons between avian and mammalian brains. This has become especially problematic for those researchers studying the neurobiology of birdsong, the largest single group within the avian neuroscience community. To deal with the many communication problems this has caused among researchers specializing in different vertebrate classes, the Avian Brain Nomenclature Forum, held at Duke University from July 18‐20, 2002, set out to develop a new terminology for the avian telencephalon and some allied brainstem cell groups. In one major step, the erroneous conception that the avian telencephalon consists mainly of a hypertrophied basal ganglia has been purged from the telencephalic terminology, and the actual parts of the basal ganglia and its brainstem afferent cell groups have been given new names to reflect their now‐evident homologies. The telencephalic regions that were incorrectly named to reflect presumed homology to mammalian basal ganglia have been renamed as parts of the pallium. The prefixes used for the new names for the pallial subdivisions have retained most established abbreviations, in an effort to maintain continuity with the pre‐existing nomenclature. Here we present a brief synopsis of the inaccuracies in the old nomenclature, a summary of the nomenclature changes, and details of changes for specific songbird vocal and auditory nuclei. We believe this new terminology will promote more accurate understanding of the broader neurobiological implications of song control mechanisms and facilitate the productive exchange of information between researchers studying avian and mammalian systems.

Long-range GABAergic projection in a circuit essential for vocal learning

The anterior forebrain pathway (AFP) in the passerine song system is essential for song learning but not for song production. Several lines of evidence suggest that area X, a major nucleus in the AFP, forms part of the avian striatum. A key feature of striatal projection neurons is that they use the inhibitory neurotransmitter γ‐aminobutyric acid (GABA). Some area X neurons express GABA‐like immunoreactivity, but the neurotransmitter phenotype of the projection neurons is largely unknown.